Ragsdale, Erik J.; Baldwin, James G.
2010-01-01
Modern morphology-based systematics, including questions of incongruence with molecular data, emphasizes analysis over similarity criteria to assess homology. Yet detailed examination of a few key characters, using new tools and processes such as computerized, three-dimensional ultrastructural reconstruction of cell complexes, can resolve apparent incongruence by re-examining primary homologies. In nematodes of Tylenchomorpha, a parasitic feeding phenotype is thus reconciled with immediate free-living outgroups. Closer inspection of morphology reveals phenotypes congruent with molecular-based phylogeny and points to a new locus of homology in mouthparts. In nematode models, the study of individually homologous cells reveals a conserved modality of evolution among dissimilar feeding apparati adapted to divergent lifestyles. Conservatism of cellular components, consistent with that of other body systems, allows meaningful comparative morphology in difficult groups of microscopic organisms. The advent of phylogenomics is synergistic with morphology in systematics, providing an honest test of homology in the evolution of phenotype. PMID:20106846
CELL-SELEX: Novel Perspectives of Aptamer-Based Therapeutics
Guo, Ke-Tai; Paul, Angela; Schichor, Christian; Ziemer, Gerhard; Wendel, Hans P.
2008-01-01
Aptamers, single stranded DNA or RNA molecules, generated by a method called SELEX (systematic evolution of ligands by exponential enrichment) have been widely used in various biomedical applications. The newly developed Cell-SELEX (cell based-SELEX) targeting whole living cells has raised great expectations for cancer biology, -therapy and regenerative medicine. Combining nanobiotechnology with aptamers, this technology opens the way to more sophisticated applications in molecular diagnosis. This paper gives a review of recent developments in SELEX technologies and new applications of aptamers. PMID:19325777
Wu, Chia-Chou; Lin, Che
2015-01-01
The induction of stem cells toward a desired differentiation direction is required for the advancement of stem cell-based therapies. Despite successful demonstrations of the control of differentiation direction, the effective use of stem cell-based therapies suffers from a lack of systematic knowledge regarding the mechanisms underlying directed differentiation. Using dynamic modeling and the temporal microarray data of three differentiation stages, three dynamic protein-protein interaction networks were constructed. The interaction difference networks derived from the constructed networks systematically delineated the evolution of interaction variations and the underlying mechanisms. A proposed relevance score identified the essential components in the directed differentiation. Inspection of well-known proteins and functional modules in the directed differentiation showed the plausibility of the proposed relevance score, with the higher scores of several proteins and function modules indicating their essential roles in the directed differentiation. During the differentiation process, the proteins and functional modules with higher relevance scores also became more specific to the neuronal identity. Ultimately, the essential components revealed by the relevance scores may play a role in controlling the direction of differentiation. In addition, these components may serve as a starting point for understanding the systematic mechanisms of directed differentiation and for increasing the efficiency of stem cell-based therapies. PMID:25977693
Towards Complex Abiotic Systems for Chemical and Biological Sensing
2009-11-01
such as phage display, cell surface display, and Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Other processes necessary to...Directed evolution by in vitro compartmentalization. Nat Methods 2006, 3, 561-570. l7Chelliserrykattil, J.; Ellington, A.D. Evolution of a T7 RNA
Eukaryotic systematics: a user's guide for cell biologists and parasitologists.
Walker, Giselle; Dorrell, Richard G; Schlacht, Alexander; Dacks, Joel B
2011-11-01
Single-celled parasites like Entamoeba, Trypanosoma, Phytophthora and Plasmodium wreak untold havoc on human habitat and health. Understanding the position of the various protistan pathogens in the larger context of eukaryotic diversity informs our study of how these parasites operate on a cellular level, as well as how they have evolved. Here, we review the literature that has brought our understanding of eukaryotic relationships from an idea of parasites as primitive cells to a crystallized view of diversity that encompasses 6 major divisions, or supergroups, of eukaryotes. We provide an updated taxonomic scheme (for 2011), based on extensive genomic, ultrastructural and phylogenetic evidence, with three differing levels of taxonomic detail for ease of referencing and accessibility (see supplementary material at Cambridge Journals On-line). Two of the most pressing issues in cellular evolution, the root of the eukaryotic tree and the evolution of photosynthesis in complex algae, are also discussed along with ideas about what the new generation of genome sequencing technologies may contribute to the field of eukaryotic systematics. We hope that, armed with this user's guide, cell biologists and parasitologists will be encouraged about taking an increasingly evolutionary point of view in the battle against parasites representing real dangers to our livelihoods and lives.
NASA Astrophysics Data System (ADS)
Terazono, Hideyuki; Kim, Hyonchol; Nomura, Fumimasa; Yasuda, Kenji
2016-06-01
We developed a microprocessing-assisted technique to select single-strand DNA aptamers that bind to unknown targets on the cell surface by modifying the conventional systematic evolution of ligands by exponential enrichment (cell-SELEX). Our technique involves 1) the specific selection of target-cell-surface-bound aptamers without leakage of intracellular components by trypsinization and 2) cloning of aptamers by microprocessing-assisted picking of single cells using magnetic beads. After cell-SELEX, the enriched aptamers were conjugated with magnetic beads. The aptamer-magnetic beads conjugates attached to target cells were collected individually by microassisted procedures using microneedles under a microscope. After that, the sequences of the collected magnetic-bead-bound aptamers were identified. As a result, a specific aptamer for the surface of target cells, e.g., human umbilical vein endothelial cells (HUVECs), was chosen and its specificity was examined using other cell types, e.g., HeLa cells. The results indicate that this microprocessing-assisted cell-SELEX method for identifying aptamers is applicable in biological research and clinical diagnostics.
Neutral null models for diversity in serial transfer evolution experiments.
Harpak, Arbel; Sella, Guy
2014-09-01
Evolution experiments with microorganisms coupled with genome-wide sequencing now allow for the systematic study of population genetic processes under a wide range of conditions. In learning about these processes in natural, sexual populations, neutral models that describe the behavior of diversity and divergence summaries have played a pivotal role. It is therefore natural to ask whether neutral models, suitably modified, could be useful in the context of evolution experiments. Here, we introduce coalescent models for polymorphism and divergence under the most common experimental evolution assay, a serial transfer experiment. This relatively simple setting allows us to address several issues that could affect diversity patterns in evolution experiments, whether selection is operating or not: the transient behavior of neutral polymorphism in an experiment beginning from a single clone, the effects of randomness in the timing of cell division and noisiness in population size in the dilution stage. In our analyses and discussion, we emphasize the implications for experiments aimed at measuring diversity patterns and making inferences about population genetic processes based on these measurements. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.
[Cell-ELA-based determination of binding affinity of DNA aptamer against U87-EGFRvIII cell].
Tan, Yan; Liang, Huiyu; Wu, Xidong; Gao, Yubo; Zhang, Xingmei
2013-05-01
A15, a DNA aptamer with binding specificity for U87 glioma cells stably overexpressing the epidermal growth factor receptor variant III (U87-EGFRvIII), was generated by cell systematic evolution of ligands by exponential enrichment (cell-SELEX) using a random nucleotide library. Subsequently, we established a cell enzyme-linked assay (cell-ELA) to detect the affinity of A15 compared to an EGFR antibody. We used A15 as a detection probe and cultured U87-EGFRvIII cells as targets. Our data indicate that the equilibrium dissociation constants (K(d)) for A15 were below 100 nmol/L and had similar affinity compared to an EGFR antibody for U87-EGFRvIII. We demonstrated that the cell-ELA was a useful method to determine the equilibrium dissociation constants (K(d)) of aptamers generated by cell-SELEX.
SELEX-Based Screening of Exosome-Tropic RNA.
Yamashita, Takuma; Shinotsuka, Haruka; Takahashi, Yuki; Kato, Kana; Nishikawa, Makiya; Takakura, Yoshinobu
2017-01-01
Cell-derived nanosized vesicles or exosomes are expected to become delivery carriers for functional RNAs, such as small interfering RNA (siRNA). A method to efficiently load functional RNAs into exosomes is required for the development of exosome-based delivery carriers of functional RNAs. However, there is no method to find exosome-tropic exogenous RNA sequences. In this study, we used a systematic evolution of ligands by exponential enrichment (SELEX) method to screen exosome-tropic RNAs that can be used to load functional RNAs into exosomes by conjugation. Pooled single stranded 80-base RNAs, each of which contains a randomized 40-base sequence, were transfected into B16-BL6 murine melanoma cells and exosomes were collected from the cells. RNAs extracted from the exosomes were subjected to next round of SELEX. Cloning and sequencing of RNAs in SELEX-screened RNA pools showed that 29 of 56 clones had a typical RNA sequence. The sequence found by SELEX was enriched in exosomes after transfection to B16-BL6 cells. The results show that the SELEX-based method can be used for screening of exosome-tropic RNAs.
Mushegyan, Vagan; Eronen, Jussi T.; Lawing, A. Michelle; Sharir, Amnon; Janis, Christine; Jernvall, Jukka; Klein, Ophir D.
2015-01-01
Summary The fossil record is widely informative about evolution, but fossils are not systematically used to study the evolution of stem cell-driven renewal. Here, we examined evolution of the continuous growth (hypselodonty) of rodent molar teeth, which is fuelled by the presence of dental stem cells. We studied occurrences of 3500 North American rodent fossils, ranging from 50 million years ago (mya) to 2 mya. We examined changes in molar height to determine if evolution of hypselodonty shows distinct patterns in the fossil record, and we found that hypselodont taxa emerged through intermediate forms of increasing crown height. Next, we designed a Markov simulation model, which replicated molar height increases throughout the Cenozoic, and, moreover, evolution of hypselodonty. Thus, by extension, the retention of the adult stem-cell niche appears to be a predictable quantitative rather than a stochastic qualitative process. Our analyses predict that hypselodonty will eventually become the dominant phenotype. PMID:25921530
Comparison of human cell signaling pathway databases—evolution, drawbacks and challenges
Chowdhury, Saikat; Sarkar, Ram Rup
2015-01-01
Elucidating the complexities of cell signaling pathways is of immense importance to gain understanding about various biological phenomenon, such as dynamics of gene/protein expression regulation, cell fate determination, embryogenesis and disease progression. The successful completion of human genome project has also helped experimental and theoretical biologists to analyze various important pathways. To advance this study, during the past two decades, systematic collections of pathway data from experimental studies have been compiled and distributed freely by several databases, which also integrate various computational tools for further analysis. Despite significant advancements, there exist several drawbacks and challenges, such as pathway data heterogeneity, annotation, regular update and automated image reconstructions, which motivated us to perform a thorough review on popular and actively functioning 24 cell signaling databases. Based on two major characteristics, pathway information and technical details, freely accessible data from commercial and academic databases are examined to understand their evolution and enrichment. This review not only helps to identify some novel and useful features, which are not yet included in any of the databases but also highlights their current limitations and subsequently propose the reasonable solutions for future database development, which could be useful to the whole scientific community. PMID:25632107
Isolation of an Aptamer that Binds Specifically to E. coli
Cleto, Fernanda; Krieger, Marco Aurélio; Cardoso, Josiane
2016-01-01
Escherichia coli is a bacterial species found ubiquitously in the intestinal flora of animals, although pathogenic variants cause major public health problems. Aptamers are short oligonucleotides that bind to targets with high affinity and specificity, and have great potential for use in diagnostics and therapy. We used cell-based Systematic Evolution of Ligands by EXponential enrichment (cell-SELEX) to isolate four single stranded DNA (ssDNA) aptamers that bind strongly to E. coli cells (ATCC generic strain 25922), with Kd values in the nanomolar range. Fluorescently labeled aptamers label the surface of E. coli cells, as viewed by fluorescent microscopy. Specificity tests with twelve different bacterial species showed that one of the aptamers–called P12-31—is highly specific for E. coli. Importantly, this aptamer binds to Meningitis/sepsis associated E. coli (MNEC) clinical isolates, and is the first aptamer described with potential for use in the diagnosis of MNEC-borne pathologies. PMID:27104834
Wang, Lingrui; Wang, Kai; Xiao, Guanjun; Zeng, Qiaoshi; Zou, Bo
2016-12-15
Organometal halide perovskites are promising materials for optoelectronic devices. Further development of these devices requires a deep understanding of their fundamental structure-property relationships. The effect of pressure on the structural evolution and band gap shifts of methylammonium lead chloride (MAPbCl 3 ) was investigated systematically. Synchrotron X-ray diffraction and Raman experiments provided structural information on the shrinkage, tilting distortion, and amorphization of the primitive cubic unit cell. In situ high pressure optical absorption and photoluminescence spectra manifested that the band gap of MAPbCl 3 could be fine-tuned to the ultraviolet region by pressure. The optical changes are correlated with pressure-induced structural evolution of MAPbCl 3 , as evidenced by band gap shifts. Comparisons between Pb-hybrid perovskites and inorganic octahedra provided insights on the effects of halogens on pressure-induced transition sequences of these compounds. Our results improve the understanding of the structural and optical properties of organometal halide perovskites.
Cnidarian Cell Type Diversity and Regulation Revealed by Whole-Organism Single-Cell RNA-Seq.
Sebé-Pedrós, Arnau; Saudemont, Baptiste; Chomsky, Elad; Plessier, Flora; Mailhé, Marie-Pierre; Renno, Justine; Loe-Mie, Yann; Lifshitz, Aviezer; Mukamel, Zohar; Schmutz, Sandrine; Novault, Sophie; Steinmetz, Patrick R H; Spitz, François; Tanay, Amos; Marlow, Heather
2018-05-31
The emergence and diversification of cell types is a leading factor in animal evolution. So far, systematic characterization of the gene regulatory programs associated with cell type specificity was limited to few cell types and few species. Here, we perform whole-organism single-cell transcriptomics to map adult and larval cell types in the cnidarian Nematostella vectensis, a non-bilaterian animal with complex tissue-level body-plan organization. We uncover eight broad cell classes in Nematostella, including neurons, cnidocytes, and digestive cells. Each class comprises different subtypes defined by the expression of multiple specific markers. In particular, we characterize a surprisingly diverse repertoire of neurons, which comparative analysis suggests are the result of lineage-specific diversification. By integrating transcription factor expression, chromatin profiling, and sequence motif analysis, we identify the regulatory codes that underlie Nematostella cell-specific expression. Our study reveals cnidarian cell type complexity and provides insights into the evolution of animal cell-specific genomic regulation. Copyright © 2018 Elsevier Inc. All rights reserved.
DNA Microarrays for Aptamer Identification and Structural Characterization
2012-09-01
appropriate vector (which has a unique set of factors affecting cloning efficiency) and transformed into competent bacterial cells to spatially...818-822. 2) Tuerk, C. and Gold, L., “Systematic Evolution of Ligands by Exponential Enrichment: RNA Ligands to Bacteriophage T4 DNA Polymerase
Predicting thunderstorm evolution using ground-based lightning detection networks
NASA Technical Reports Server (NTRS)
Goodman, Steven J.
1990-01-01
Lightning measurements acquired principally by a ground-based network of magnetic direction finders are used to diagnose and predict the existence, temporal evolution, and decay of thunderstorms over a wide range of space and time scales extending over four orders of magnitude. The non-linear growth and decay of thunderstorms and their accompanying cloud-to-ground lightning activity is described by the three parameter logistic growth model. The growth rate is shown to be a function of the storm size and duration, and the limiting value of the total lightning activity is related to the available energy in the environment. A new technique is described for removing systematic bearing errors from direction finder data where radar echoes are used to constrain site error correction and optimization (best point estimate) algorithms. A nearest neighbor pattern recognition algorithm is employed to cluster the discrete lightning discharges into storm cells and the advantages and limitations of different clustering strategies for storm identification and tracking are examined.
Biological information systems: Evolution as cognition-based information management.
Miller, William B
2018-05-01
An alternative biological synthesis is presented that conceptualizes evolutionary biology as an epiphenomenon of integrated self-referential information management. Since all biological information has inherent ambiguity, the systematic assessment of information is required by living organisms to maintain self-identity and homeostatic equipoise in confrontation with environmental challenges. Through their self-referential attachment to information space, cells are the cornerstone of biological action. That individualized assessment of information space permits self-referential, self-organizing niche construction. That deployment of information and its subsequent selection enacted the dominant stable unicellular informational architectures whose biological expressions are the prokaryotic, archaeal, and eukaryotic unicellular forms. Multicellularity represents the collective appraisal of equivocal environmental information through a shared information space. This concerted action can be viewed as systematized information management to improve information quality for the maintenance of preferred homeostatic boundaries among the varied participants. When reiterated in successive scales, this same collaborative exchange of information yields macroscopic organisms as obligatory multicellular holobionts. Cognition-Based Evolution (CBE) upholds that assessment of information precedes biological action, and the deployment of information through integrative self-referential niche construction and natural cellular engineering antecedes selection. Therefore, evolutionary biology can be framed as a complex reciprocating interactome that consists of the assessment, communication, deployment and management of information by self-referential organisms at multiple scales in continuous confrontation with environmental stresses. Copyright © 2017 Elsevier Ltd. All rights reserved.
Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution.
Vierstra, Jeff; Rynes, Eric; Sandstrom, Richard; Zhang, Miaohua; Canfield, Theresa; Hansen, R Scott; Stehling-Sun, Sandra; Sabo, Peter J; Byron, Rachel; Humbert, Richard; Thurman, Robert E; Johnson, Audra K; Vong, Shinny; Lee, Kristen; Bates, Daniel; Neri, Fidencio; Diegel, Morgan; Giste, Erika; Haugen, Eric; Dunn, Douglas; Wilken, Matthew S; Josefowicz, Steven; Samstein, Robert; Chang, Kai-Hsin; Eichler, Evan E; De Bruijn, Marella; Reh, Thomas A; Skoultchi, Arthur; Rudensky, Alexander; Orkin, Stuart H; Papayannopoulou, Thalia; Treuting, Piper M; Selleri, Licia; Kaul, Rajinder; Groudine, Mark; Bender, M A; Stamatoyannopoulos, John A
2014-11-21
To study the evolutionary dynamics of regulatory DNA, we mapped >1.3 million deoxyribonuclease I-hypersensitive sites (DHSs) in 45 mouse cell and tissue types, and systematically compared these with human DHS maps from orthologous compartments. We found that the mouse and human genomes have undergone extensive cis-regulatory rewiring that combines branch-specific evolutionary innovation and loss with widespread repurposing of conserved DHSs to alternative cell fates, and that this process is mediated by turnover of transcription factor (TF) recognition elements. Despite pervasive evolutionary remodeling of the location and content of individual cis-regulatory regions, within orthologous mouse and human cell types the global fraction of regulatory DNA bases encoding recognition sites for each TF has been strictly conserved. Our findings provide new insights into the evolutionary forces shaping mammalian regulatory DNA landscapes. Copyright © 2014, American Association for the Advancement of Science.
Soft gluon evolution and non-global logarithms
NASA Astrophysics Data System (ADS)
Martínez, René Ángeles; De Angelis, Matthew; Forshaw, Jeffrey R.; Plätzer, Simon; Seymour, Michael H.
2018-05-01
We consider soft-gluon evolution at the amplitude level. Our evolution algorithm applies to generic hard-scattering processes involving any number of coloured partons and we present a reformulation of the algorithm in such a way as to make the cancellation of infrared divergences explicit. We also emphasise the special role played by a Lorentz-invariant evolution variable, which coincides with the transverse momentum of the latest emission in a suitably defined dipole zero-momentum frame. Handling large colour matrices presents the most significant challenge to numerical implementations and we present a means to expand systematically about the leading colour approximation. Specifically, we present a systematic procedure to calculate the resulting colour traces, which is based on the colour flow basis. Identifying the leading contribution leads us to re-derive the Banfi-Marchesini-Smye equation. However, our formalism is more general and can systematically perform resummation of contributions enhanced by the t'Hooft coupling α s N ˜ 1, along with successive perturbations that are parametrically suppressed by powers of 1 /N . We also discuss how our approach relates to earlier work.
Gurzu, Simona; Beleaua, Marius Alexandru; Jung, Ioan
2018-01-01
To reveal the particular aspects of the tumor microenvironment of malignant melanomas, a systematic review including 34 representative papers was performed. The review took into account the aspects related the Wnt/β-catenin pathway-related epithelial-mesenchymal transition (EMT) versus mesenchymal-epithelial transition (MET) of keratinocytes, fibroblasts and melanoma cells, as possible tools for understanding genesis and evolution of malignant melanoma. The possible reversible features of EMT and the role of tumor microenvironment in the metastatic process were also analyzed. A particular issue was related on the cancer stem cells that include melanocyte stem cells (McSCs) and multipotent mesenchymal stem/stromal cells (MSCs). As the McSCs embryological development in mouse is not similar to human development, the role of stem cells in genesis and development of human melanoma should be proved in human melanoma cells only. For further development of targeted therapy, a better understanding of melanomagenesis pathways and its microenvironment particularities is necessary.
Basourakos, Spyridon P.; Li, Likun; Aparicio, Ana M.; Corn, Paul G.; Kim, Jeri; Thompson, Timothy C.
2017-01-01
Maintenance of genomic stability is a critical determinant of cell survival and is necessary for growth and progression of malignant cells. Interstrand crosslinking (ICL) agents, including platinum-based agents, are first-line chemotherapy treatment for many solid human cancers. In malignant cells, ICL triggers the DNA damage response (DDR). When the damage burden is high and lesions cannot be repaired, malignant cells are unable to divide and ultimately undergo cell death either through mitotic catastrophe or apoptosis. The activities of ICL agents, in particular platinum-based therapies, establish a “molecular landscape,” i.e., a pattern of DNA damage that can potentially be further exploited therapeutically with DDR-targeting agents. If the molecular landscape created by platinum-based agents could be better defined at the molecular level, a systematic, mechanistic rationale(s) could be developed for the use of DDR-targeting therapies in combination/maintenance protocols for specific, clinically advanced malignancies. New therapeutic drugs such as poly(ADP-ribose) polymerase (PARP) inhibitors are examples of DDR-targeting therapies that could potentially increase the DNA damage and replication stress imposed by platinum-based agents in tumor cells and provide therapeutic benefit for patients with advanced malignancies. Recent studies have shown that the use of PARP inhibitors together with platinum-based agents is a promising therapy strategy for ovarian cancer patients with ”BRCAness”, i.e., a phenotypic characteristic of tumors that not only can involve loss-of-function mutations in either BRCA1 or BRCA2, but also encompasses the molecular features of BRCA-mutant tumors. On the basis of these promising results, additional mechanism-based studies focused on the use of various DDR-targeting therapies in combination with platinum-based agents should be considered. This review discusses, in general, (1) ICL agents, primarily platinum-based agents, that establish a molecular landscape that can be further exploited therapeutically; (2) multiple points of potential intervention after ICL agent–induced crosslinking that further predispose to cell death and can be incorporated into a systematic, therapeutic rationale for combination/maintenance therapy using DDR-targeting agents; and (3) available agents that can be considered for use in combination/maintenance clinical protocols with platinum-based agents for patients with advanced malignancies. PMID:27978798
Basourakos, Spyridon P; Li, Likun; Aparicio, Ana M; Corn, Paul G; Kim, Jeri; Thompson, Timothy C
2017-01-01
Maintenance of genomic stability is a critical determinant of cell survival and is necessary for growth and progression of malignant cells. Interstrand crosslinking (ICL) agents, including platinum-based agents, are first-line chemotherapy treatment for many solid human cancers. In malignant cells, ICL triggers the DNA damage response (DDR). When the damage burden is high and lesions cannot be repaired, malignant cells are unable to divide and ultimately undergo cell death either through mitotic catastrophe or apoptosis. The activities of ICL agents, in particular platinum-based therapies, establish a "molecular landscape," i.e., a pattern of DNA damage that can potentially be further exploited therapeutically with DDR-targeting agents. If the molecular landscape created by platinum-based agents could be better defined at the molecular level, a systematic, mechanistic rationale(s) could be developed for the use of DDR-targeting therapies in combination/maintenance protocols for specific, clinically advanced malignancies. New therapeutic drugs such as poly(ADP-ribose) polymerase (PARP) inhibitors are examples of DDR-targeting therapies that could potentially increase the DNA damage and replication stress imposed by platinum-based agents in tumor cells and provide therapeutic benefit for patients with advanced malignancies. Recent studies have shown that the use of PARP inhibitors together with platinum-based agents is a promising therapy strategy for ovarian cancer patients with "BRCAness", i.e., a phenotypic characteristic of tumors that not only can involve loss-of-function mutations in either BRCA1 or BRCA2, but also encompasses the molecular features of BRCA-mutant tumors. On the basis of these promising results, additional mechanism-based studies focused on the use of various DDR-targeting therapies in combination with platinum-based agents should be considered. This review discusses, in general, (1) ICL agents, primarily platinum-based agents, that establish a molecular landscape that can be further exploited therapeutically; (2) multiple points of potential intervention after ICL agent-induced crosslinking that further predispose to cell death and can be incorporated into a systematic, therapeutic rationale for combination/ maintenance therapy using DDR-targeting agents; and (3) available agents that can be considered for use in combination/maintenance clinical protocols with platinum-based agents for patients with advanced malignancies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Herculano-Houzel, Suzana; Manger, Paul R.; Kaas, Jon H.
2014-01-01
Enough species have now been subject to systematic quantitative analysis of the relationship between the morphology and cellular composition of their brain that patterns begin to emerge and shed light on the evolutionary path that led to mammalian brain diversity. Based on an analysis of the shared and clade-specific characteristics of 41 modern mammalian species in 6 clades, and in light of the phylogenetic relationships among them, here we propose that ancestral mammal brains were composed and scaled in their cellular composition like modern afrotherian and glire brains: with an addition of neurons that is accompanied by a decrease in neuronal density and very little modification in glial cell density, implying a significant increase in average neuronal cell size in larger brains, and the allocation of approximately 2 neurons in the cerebral cortex and 8 neurons in the cerebellum for every neuron allocated to the rest of brain. We also propose that in some clades the scaling of different brain structures has diverged away from the common ancestral layout through clade-specific (or clade-defining) changes in how average neuronal cell mass relates to numbers of neurons in each structure, and how numbers of neurons are differentially allocated to each structure relative to the number of neurons in the rest of brain. Thus, the evolutionary expansion of mammalian brains has involved both concerted and mosaic patterns of scaling across structures. This is, to our knowledge, the first mechanistic model that explains the generation of brains large and small in mammalian evolution, and it opens up new horizons for seeking the cellular pathways and genes involved in brain evolution. PMID:25157220
Molecular Recognition of Human Liver Cancer Cells Using DNA Aptamers Generated via Cell-SELEX.
Xu, Jiehua; Teng, I-Ting; Zhang, Liqin; Delgado, Stefanie; Champanhac, Carole; Cansiz, Sena; Wu, Cuichen; Shan, Hong; Tan, Weihong
2015-01-01
Most clinical cases of liver cancer cannot be diagnosed until they have evolved to an advanced stage, thus resulting in high mortality. It is well recognized that the implementation of early detection methods and the development of targeted therapies for liver cancer are essential to reducing the high mortality rates associated with this disease. To achieve these goals, molecular probes capable of recognizing liver cancer cell-specific targets are needed. Here we describe a panel of aptamers able to distinguish hepatocarcinoma from normal liver cells. The aptamers, which were selected by cell-based SELEX (Systematic Evolution of Ligands by Exponential Enrichment), have Kd values in the range of 64-349 nM toward the target human hepatoma cell HepG2, and also recognize ovarian cancer cells and lung adenocarcinoma. The proteinase treatment experiment indicated that all aptamers could recognize target HepG2 cells through surface proteins. This outcome suggested that these aptamers could be used as potential probes for further research in cancer studies, such as developing early detection assays, targeted therapies, and imaging agents, as well as for the investigation of common membrane proteins in these distinguishable cancers.
Evolution of early embryogenesis in rhabditid nematodes
Brauchle, Michael; Kiontke, Karin; MacMenamin, Philip; Fitch, David H. A.; Piano, Fabio
2009-01-01
The cell biological events that guide early embryonic development occur with great precision within species but can be quite diverse across species. How these cellular processes evolve and which molecular components underlie evolutionary changes is poorly understood. To begin to address these questions, we systematically investigated early embryogenesis, from the one- to the four-cell embryo, in 34 nematode species related to C. elegans. We found 40 cell-biological characters that captured the phenotypic differences between these species. By tracing the evolutionary changes on a molecular phylogeny, we found that these characters evolved multiple times and independently of one another. Strikingly, all these phenotypes are mimicked by single-gene RNAi experiments in C. elegans. We use these comparisons to hypothesize the molecular mechanisms underlying the evolutionary changes. For example, we predict that a cell polarity module was altered during the evolution of the Protorhabditis group and show that PAR-1, a kinase localized asymmetrically in C. elegans early embryos, is symmetrically localized in the one-cell stage of Protorhabditis group species. Our genome-wide approach identifies candidate molecules—and thereby modules—associated with evolutionary changes in cell-biological phenotypes. PMID:19643102
Tsiba, J B; Mpemba-Loufoua, A B; Makosso, E; Nzingoula, S
2007-02-01
The authors report two cases of hydocholecystis causing abdominal pains in the sickle cell child. The patients were two girls aged respectively 4 and 12. Hydrocholecystis is defined by acute distension of the gallbladder The diagnosis was made by scan which allowed to follow the evolution in the two sickle cell children. After two crises, no more recurrence was noted in the first patient, on the other hand in the second child recurrences became more frequent. Some authors indicate surgery systematically while others recommend it only after several recurrences.
Evolutionary Cell Biology of Proteins from Protists to Humans and Plants.
Plattner, Helmut
2018-03-01
During evolution, the cell as a fine-tuned machine had to undergo permanent adjustments to match changes in its environment, while "closed for repair work" was not possible. Evolution from protists (protozoa and unicellular algae) to multicellular organisms may have occurred in basically two lineages, Unikonta and Bikonta, culminating in mammals and angiosperms (flowering plants), respectively. Unicellular models for unikont evolution are myxamoebae (Dictyostelium) and increasingly also choanoflagellates, whereas for bikonts, ciliates are preferred models. Information accumulating from combined molecular database search and experimental verification allows new insights into evolutionary diversification and maintenance of genes/proteins from protozoa on, eventually with orthologs in bacteria. However, proteins have rarely been followed up systematically for maintenance or change of function or intracellular localization, acquirement of new domains, partial deletion (e.g. of subunits), and refunctionalization, etc. These aspects are discussed in this review, envisaging "evolutionary cell biology." Protozoan heritage is found for most important cellular structures and functions up to humans and flowering plants. Examples discussed include refunctionalization of voltage-dependent Ca 2+ channels in cilia and replacement by other types during evolution. Altogether components serving Ca 2+ signaling are very flexible throughout evolution, calmodulin being a most conservative example, in contrast to calcineurin whose catalytic subunit is lost in plants, whereas both subunits are maintained up to mammals for complex functions (immune defense and learning). Domain structure of R-type SNAREs differs in mono- and bikonta, as do Ca 2+ -dependent protein kinases. Unprecedented selective expansion of the subunit a which connects multimeric base piece and head parts (V0, V1) of H + -ATPase/pump may well reflect the intriguing vesicle trafficking system in ciliates, specifically in Paramecium. One of the most flexible proteins is centrin when its intracellular localization and function throughout evolution is traced. There are many more examples documenting evolutionary flexibility of translation products depending on requirements and potential for implantation within the actual cellular context at different levels of evolution. From estimates of gene and protein numbers per organism, it appears that much of the basic inventory of protozoan precursors could be transmitted to highest eukaryotic levels, with some losses and also with important additional "inventions." © 2017 The Author(s) Journal of Eukaryotic Microbiology © 2017 International Society of Protistologists.
Cell specific aptamer-photosensitizer conjugates as a molecular tool in photodynamic therapy
Mallikaratchy, Prabodhika; Tang, Zhiwen
2010-01-01
This paper describes the application of a molecular construct of a photosensitizer and an aptamer for photo-therapeutically targeting tumor cells. The key step in increasing selectivity in chemotherapeutic drugs is to create effective molecular platforms that could target cancer cells but not normal cells. Recently, we have developed a strategy via cell-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) to obtain cell specific aptamers using intact viable cells as targets to select aptamers that can recognize cell membrane proteins with high selectivity and excellent affinity. We have identified an aptamer TD05 that only recognizes Ramos cells, a Burkitt’s lymphoma cell line. Here, the high specificity of aptamers in target cell binding and an efficient phototherapy reagent, Ce6, are molecularly engineered to construct a highly selective Aptamer-photosensitizer conjugates (APS) to effectively destroy target cancer cells. Introduction of the APS conjugates followed by irradiation of light selectively destroyed target Ramos cells but not acute lymphoblastic leukemia and myeloid leukemia cell lines. This study demonstrates that the use of cancer specific aptamers conjugated to a photosensitizer will enhance the selectivity of photodynamic therapy. Coupled with the advantages of the cell-SELEX in generating multiple effective aptamers for diseased cell recognition, we will be able to develop highly efficient photosensitizer based therapeutical reagents for clinical applications. PMID:18058891
He, M; Callanan, A; Lagaras, K; Steele, J A M; Stevens, M M
2017-08-01
Renal transplantation is well established as the optimal form of renal replacement therapy but is restricted by the limited pool of organs available for transplantation. The whole organ decellularisation approach is leading the way for a regenerative medicine solution towards bioengineered organ replacements. However, systematic preoptimization of both decellularization and recellularization parameters is essential prior to any potential clinical application and should be the next stage in the evolution of whole organ decellularization as a potential strategy for bioengineered organ replacements. Here we have systematically assessed two fundamental parameters (concentration and duration of perfusion) with regards to the effects of differing exposure to the most commonly used single decellularizing agent (sodium dodecyl sulphate/SDS) in the perfusion decellularization process for whole rat kidney ECM bioscaffolds, with findings showing improved preservation of both structural and functional components of the whole kidney ECM bioscaffold. Whole kidney bioscaffolds based on our enhanced protocol were successfully recellularized with rat primary renal cells and mesenchymal stromal cells. These findings should be widely applicable to decellularized whole organ bioscaffolds and their optimization in the development of regenerated organ replacements for transplantation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1352-1360, 2017. © 2016 Wiley Periodicals, Inc.
Huang, Yukun; Wang, Xin; Duan, Nuo; Xia, Yu; Wang, Zhouping; Che, Zhenming; Wang, Lijun; Yang, Xiao; Chen, Xianggui
2018-06-15
An aptamer against Streptococcus pyogenes was selected and identified, and a fluorescent method based on the reported aptamer was established to detect S. pyogenes in the cooked chicken. Through a twelve rounds of whole-bacterium SELEX (systematic evolution of ligands by exponential enrichment) selection in vitro, a set of aptamers binding to the whole cell of S. pyogenes were generated, harvesting a low-level dissociation constant (K d ) value of 44 ± 5 nmol L -1 of aptamer S-12. Aptamer-based quantification of S. pyogenes in the cooked chicken sample was implemented in a fluorescence resonance energy transfer-based assay by using graphene oxide, resulting in a limit of detection of 70 cfu mL -1 . The selected aptamer showed affinity and selectivity recognizing S. pyogenes; besides, more biosensors based on the selected aptamer as a molecular recognition element could be developed in the innovative determinations of S. pyogenes. Copyright © 2018 Elsevier Inc. All rights reserved.
Aptamer-based viability impedimetric sensor for bacteria.
Labib, Mahmoud; Zamay, Anna S; Kolovskaya, Olga S; Reshetneva, Irina T; Zamay, Galina S; Kibbee, Richard J; Sattar, Syed A; Zamay, Tatiana N; Berezovski, Maxim V
2012-11-06
The development of an aptamer-based viability impedimetric sensor for bacteria (AptaVISens-B) is presented. Highly specific DNA aptamers to live Salmonella typhimurium were selected via the cell-systematic evolution of ligands by exponential enrichment (SELEX) technique. Twelve rounds of selection were performed; each comprises a positive selection step against viable S. typhimurium and a negative selection step against heat killed S. typhimurium and a mixture of related pathogens, including Salmonella enteritidis, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Citrobacter freundii to ensure the species specificity of the selected aptamers. The DNA sequence showing the highest binding affinity to the bacteria was further integrated into an impedimetric sensor via self-assembly onto a gold nanoparticle-modified screen-printed carbon electrode (GNP-SPCE). Remarkably, this aptasensor is highly selective and can successfully detect S. typhimurium down to 600 CFU mL(-1) (equivalent to 18 live cells in 30 μL of assay volume) and distinguish it from other Salmonella species, including S. enteritidis and S. choleraesuis. This report is envisaged to open a new venue for the aptamer-based viability sensing of a variety of microorganisms, particularly viable but nonculturable (VBNC) bacteria, using a rapid, economic, and label-free electrochemical platform.
Schiff Base as Additive for Preventing Gas Evolution in Li4Ti5O12-Based Lithium-Ion Battery.
Daigle, Jean-Christophe; Asakawa, Yuichiro; Hovington, Pierre; Zaghib, Karim
2017-11-29
Lithium titanium oxide (Li 4 Ti 5 O 12 )-based electrodes are very promising for long-life cycle batteries. However, the surface reactivity of Li 4 Ti 5 O 12 in organic electrolytes leading to gas evolution is still a problem that may cause expansion of pouch cells. In this study, we report the use of Schiff base (1,8-diazabicyclo[5.4.0]undec-7-ene) as an additive that prevents gas evolution during cell aging by a new mechanism involving the solid electrolyte interface on the anode surface. The in situ ring opening polymerization of cyclic carbonates occurs during the first cycles to decrease gas evolution by 9.7 vol % without increasing the internal resistance of the battery.
DNA aptamer-based colorimetric detection platform for Salmonella Enteritidis.
Bayraç, Ceren; Eyidoğan, Füsun; Avni Öktem, Hüseyin
2017-12-15
Food safety is a major issue to protect public health and a key challenge is to find detection methods for identification of hazards in food. Food borne infections affects millions of people each year and among pathogens, Salmonella Enteritidis is most widely found bacteria causing food borne diseases. Therefore, simple, rapid, and specific detection methods are needed for food safety. In this study, we demonstrated the selection of DNA aptamers with high affinity and specificity against S. Enteritidis via Cell Systematic Evolution of Ligands by Exponential Enrichment (Cell-SELEX) and development of sandwich type aptamer-based colorimetric platforms for its detection. Two highly specific aptamers, crn-1 and crn-2, were developed through 12 rounds of selection with K d of 0.971µM and 0.309µM, respectively. Both aptamers were used to construct sandwich type capillary detection platforms. With the detection limit of 10 3 CFU/mL, crn-1 and crn-2 based platforms detected target bacteria specifically based on color change. This platform is also suitable for detection of S. Enteritidis in complex food matrix. Thus, this is the first to demonstrate use of Salmonella aptamers for development of the colorimetric aptamer-based detection platform in its identification and detection with naked eye in point-of-care. Copyright © 2017 Elsevier B.V. All rights reserved.
Repar, Jelena; Warnecke, Tobias
2017-08-01
Inversions are a major contributor to structural genome evolution in prokaryotes. Here, using a novel alignment-based method, we systematically compare 1,651 bacterial and 98 archaeal genomes to show that inversion landscapes are frequently biased toward (symmetric) inversions around the origin-terminus axis. However, symmetric inversion bias is not a universal feature of prokaryotic genome evolution but varies considerably across clades. At the extremes, inversion landscapes in Bacillus-Clostridium and Actinobacteria are dominated by symmetric inversions, while there is little or no systematic bias favoring symmetric rearrangements in archaea with a single origin of replication. Within clades, we find strong but clade-specific relationships between symmetric inversion bias and different features of adaptive genome architecture, including the distance of essential genes to the origin of replication and the preferential localization of genes on the leading strand. We suggest that heterogeneous selection pressures have converged to produce similar patterns of structural genome evolution across prokaryotes. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
[Analysis of the implementation of Nursing Assistance Systematization in a rehabilitation unit].
Neves, Rinaldo de Souza; Shimizu, Helena Eri
2010-01-01
This study seeks to analyze the execution of the Infirmary Attendance Systematization Nursing stages through an exploratory, qualitative and retrospective approach. The retrospective analysis took place using 25 medic reports containing 25 historical reports, 12 diagnosis reports, 100 prescriptions and 100 nursing evolution reports. The results demonstrated the many difficulties the nurses faced to make Nursing Assistance Systematization operational. Although all Nursing Assistance Systematization stages were accomplished - historical, diagnosis, prescription, evolution and nursing - it was verified a larger frequency in filling prescription and historical related forms and a lesser one related with evolution and diagnosis related forms. In short, Nursing Assistance Systematization procedures still are fragmentized, showing the need to reorganize this attendance methodology attendance, and, above all, to invest in continuous nursing training to improve the customer care services quality.
Wang, Zhangwei; Baker, Ian; Cai, Zhonghou; ...
2016-09-01
A systematic study of the effects of up to 1.1 at. % carbon on the mechanical properties and evolution of the dislocation substructure in a series of a high entropy alloys (HEA) based on Fe 40.4Ni 11.3Mn 34.8Al 7.5Cr 6 is presented. Transmission electron microscopy (TEM), synchrotron X-ray diffraction (XRD) and atom probe tomography (APT) were used to show that all the alloys are single-phase f.c.c. random solid solutions. The lattice constant, determined from synchrotron XRD measurements, increases linearly with increasing carbon concentration, which leads to a linear relationship between the yield strength and the carbon concentration. The dislocation substructures,more » as determined by a TEM, show a transition from wavy slip to planar slip and, at higher strains, and from cell-forming structure (dislocations cells, cell blocks and dense dislocation walls) to non-cell forming structure (Taylor lattice, microbands and domain boundaries) with the addition of carbon, features related to the increase in lattice friction stress. The stacking fault energy (measured via weak-beam imaging of the separation of dislocation partials) decreases with increasing carbon content, which also contributes to the transition from wavy slip to planar slip. The formation of non-cell forming structure induced by carbon leads to a high degree of strain hardening and a substantial increase in the ultimate tensile strength. In conclusion, the consequent postponement of necking due to the high strain hardening, along with the plasticity accommodation arising from the formation of microbands and domain boundaries, result in an increase of ductility due to the carbon addition.« less
2007-08-01
Archaeology, University of California, Los Angeles. Kennett, Douglas J. 1998 Behavioral Ecology and the Evolution of Hunter-Gatherer Societies on the...Systematics and Ecology , Department of Ecology , Evolution , and Marine Biology, University of California Santa Barbara. Environmental report No. 10...be anticipated; housing residents would be provided with information on types of native plants that can be used for landscaping to avoid the
Compression and release dynamics of an active matter system of Euglena gracilis
NASA Astrophysics Data System (ADS)
Lam, Amy; Tsang, Alan C. H.; Ouellette, Nicholas; Riedel-Kruse, Ingmar
Active matter, defined as ensembles of self-propelled particles, encompasses a large variety of systems at all scales, from nanoparticles to bird flocks. Though various models and simulations have been created to describe the dynamics of these systems, experimental verification has been difficult to obtain. This is frequently due to the complex interaction rules which govern the particle behavior, in turn making systematic varying of parameters impossible. Here, we propose a model for predicting the system evolution of compression and release of an active system based on experiments and simulations. In particular, we consider ensembles of the unicellular, photo-responsive algae, Euglena gracilis, under light stimulation. By varying the spatiotemporal light patterns, we are able to finely adjust cell densities and achieve arbitrary non-homogeneous distributions, including compression into high-density aggregates of varying geometries. We observe the formation of depletion zones after the release of the confining stimulus and investigate the effects of the density distribution and particle rotational noise on the depletion. These results provide implications for defining state parameters which determine system evolution.
Mathematical modeling of the malignancy of cancer using graph evolution.
Gunduz-Demir, Cigdem
2007-10-01
We report a novel computational method based on graph evolution process to model the malignancy of brain cancer called glioma. In this work, we analyze the phases that a graph passes through during its evolution and demonstrate strong relation between the malignancy of cancer and the phase of its graph. From the photomicrographs of tissues, which are diagnosed as normal, low-grade cancerous and high-grade cancerous, we construct cell-graphs based on the locations of cells; we probabilistically generate an edge between every pair of cells depending on the Euclidean distance between them. For a cell-graph, we extract connectivity information including the properties of its connected components in order to analyze the phase of the cell-graph. Working with brain tissue samples surgically removed from 12 patients, we demonstrate that cell-graphs generated for different tissue types evolve differently and that they exhibit different phase properties, which distinguish a tissue type from another.
The evolution of culture (or the lack thereof): mapping the conceptual space.
Gadagkar, Raghavendra
2017-07-01
This short essay is based on a lecture that I gave at short notice on a subject in which I am by no means an expert. The combination of lack of expertise and time for preparation, created an unexpectedly unique opportunity for thinking outside the box. I decided not to try to read up (as there was no time in any case) but instead to organize the little that I already knew about cultural evolution in a systematic schema-I attempted to create a scaffolding, on which I could hang everything I knew about cultural evolution, and hopefully, everything I might ever discover about cultural evolution in the future. I considered three dimensions of the study of cultural evolution, namely (i) the phenomenon of cultural evolution, (ii) production of knowledge in the field of cultural evolution, and (iii) the consequences or applications of an understanding of the evolution of culture.
Biotechnological approaches to study plant responses to stress.
Pérez-Clemente, Rosa M; Vives, Vicente; Zandalinas, Sara I; López-Climent, María F; Muñoz, Valeria; Gómez-Cadenas, Aurelio
2013-01-01
Multiple biotic and abiotic environmental stress factors affect negatively various aspects of plant growth, development, and crop productivity. Plants, as sessile organisms, have developed, in the course of their evolution, efficient strategies of response to avoid, tolerate, or adapt to different types of stress situations. The diverse stress factors that plants have to face often activate similar cell signaling pathways and cellular responses, such as the production of stress proteins, upregulation of the antioxidant machinery, and accumulation of compatible solutes. Over the last few decades advances in plant physiology, genetics, and molecular biology have greatly improved our understanding of plant responses to abiotic stress conditions. In this paper, recent progresses on systematic analyses of plant responses to stress including genomics, proteomics, metabolomics, and transgenic-based approaches are summarized.
Biotechnological Approaches to Study Plant Responses to Stress
Pérez-Clemente, Rosa M.; Vives, Vicente; Zandalinas, Sara I.; López-Climent, María F.; Muñoz, Valeria; Gómez-Cadenas, Aurelio
2013-01-01
Multiple biotic and abiotic environmental stress factors affect negatively various aspects of plant growth, development, and crop productivity. Plants, as sessile organisms, have developed, in the course of their evolution, efficient strategies of response to avoid, tolerate, or adapt to different types of stress situations. The diverse stress factors that plants have to face often activate similar cell signaling pathways and cellular responses, such as the production of stress proteins, upregulation of the antioxidant machinery, and accumulation of compatible solutes. Over the last few decades advances in plant physiology, genetics, and molecular biology have greatly improved our understanding of plant responses to abiotic stress conditions. In this paper, recent progresses on systematic analyses of plant responses to stress including genomics, proteomics, metabolomics, and transgenic-based approaches are summarized. PMID:23509757
Interspecies Chimerism with Mammalian Pluripotent Stem Cells.
Wu, Jun; Platero-Luengo, Aida; Sakurai, Masahiro; Sugawara, Atsushi; Gil, Maria Antonia; Yamauchi, Takayoshi; Suzuki, Keiichiro; Bogliotti, Yanina Soledad; Cuello, Cristina; Morales Valencia, Mariana; Okumura, Daiji; Luo, Jingping; Vilariño, Marcela; Parrilla, Inmaculada; Soto, Delia Alba; Martinez, Cristina A; Hishida, Tomoaki; Sánchez-Bautista, Sonia; Martinez-Martinez, M Llanos; Wang, Huili; Nohalez, Alicia; Aizawa, Emi; Martinez-Redondo, Paloma; Ocampo, Alejandro; Reddy, Pradeep; Roca, Jordi; Maga, Elizabeth A; Esteban, Concepcion Rodriguez; Berggren, W Travis; Nuñez Delicado, Estrella; Lajara, Jeronimo; Guillen, Isabel; Guillen, Pedro; Campistol, Josep M; Martinez, Emilio A; Ross, Pablo Juan; Izpisua Belmonte, Juan Carlos
2017-01-26
Interspecies blastocyst complementation enables organ-specific enrichment of xenogenic pluripotent stem cell (PSC) derivatives. Here, we establish a versatile blastocyst complementation platform based on CRISPR-Cas9-mediated zygote genome editing and show enrichment of rat PSC-derivatives in several tissues of gene-edited organogenesis-disabled mice. Besides gaining insights into species evolution, embryogenesis, and human disease, interspecies blastocyst complementation might allow human organ generation in animals whose organ size, anatomy, and physiology are closer to humans. To date, however, whether human PSCs (hPSCs) can contribute to chimera formation in non-rodent species remains unknown. We systematically evaluate the chimeric competency of several types of hPSCs using a more diversified clade of mammals, the ungulates. We find that naïve hPSCs robustly engraft in both pig and cattle pre-implantation blastocysts but show limited contribution to post-implantation pig embryos. Instead, an intermediate hPSC type exhibits higher degree of chimerism and is able to generate differentiated progenies in post-implantation pig embryos. Copyright © 2017 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Joyce, Meridith; Chaboyer, Brian
2016-01-01
Synthetic Red Giant Branch Bump (RGBB) magnitudes are generated with the most recent theoretical stellar evolution models computed with the Dartmouth Stellar Evolution Program (DSEP) code. They are compared to the observational work of Nataf et al. (2013), who present RGBB magnitudes for 72 globular clusters. A DSEP model using a chemical composition with enhanced α capture [α/Fe] =+0.4 and an age of 13 Gyr shows agreement with observations over metallicities ranging from [Fe/H] = 0 to [Fe/H] ≈-1.5, with discrepancy emerging at lower metallicities. A model-independent, density-based outlier detection routine known as the Local Outlying Factor (LOF) algorithm is applied to the observations in order to identify clusters that deviate most in magnitude-metallicity space from the bulk of the observations. Our model's fit is scrutinized with a series of χ^2 routines performed on subsets of the data from which highly anomalous clusters have been selectively removed based on LOF identification. In particular, NGCs 6254, 6681, 6218, and 1904 are tagged recurrently as outliers. The effects of systematic and non-systematic error in metallicity are assessed, and the robustness of observational error bars is investigated.
Stochastic damage evolution in textile laminates
NASA Technical Reports Server (NTRS)
Dzenis, Yuris A.; Bogdanovich, Alexander E.; Pastore, Christopher M.
1993-01-01
A probabilistic model utilizing random material characteristics to predict damage evolution in textile laminates is presented. Model is based on a division of each ply into two sublaminas consisting of cells. The probability of cell failure is calculated using stochastic function theory and maximal strain failure criterion. Three modes of failure, i.e. fiber breakage, matrix failure in transverse direction, as well as matrix or interface shear cracking, are taken into account. Computed failure probabilities are utilized in reducing cell stiffness based on the mesovolume concept. A numerical algorithm is developed predicting the damage evolution and deformation history of textile laminates. Effect of scatter of fiber orientation on cell properties is discussed. Weave influence on damage accumulation is illustrated with the help of an example of a Kevlar/epoxy laminate.
Repar, Jelena; Warnecke, Tobias
2017-01-01
Abstract Inversions are a major contributor to structural genome evolution in prokaryotes. Here, using a novel alignment-based method, we systematically compare 1,651 bacterial and 98 archaeal genomes to show that inversion landscapes are frequently biased toward (symmetric) inversions around the origin–terminus axis. However, symmetric inversion bias is not a universal feature of prokaryotic genome evolution but varies considerably across clades. At the extremes, inversion landscapes in Bacillus–Clostridium and Actinobacteria are dominated by symmetric inversions, while there is little or no systematic bias favoring symmetric rearrangements in archaea with a single origin of replication. Within clades, we find strong but clade-specific relationships between symmetric inversion bias and different features of adaptive genome architecture, including the distance of essential genes to the origin of replication and the preferential localization of genes on the leading strand. We suggest that heterogeneous selection pressures have converged to produce similar patterns of structural genome evolution across prokaryotes. PMID:28407093
Phenotypic Heterogeneity and the Evolution of Bacterial Life Cycles.
van Gestel, Jordi; Nowak, Martin A
2016-02-01
Most bacteria live in colonies, where they often express different cell types. The ecological significance of these cell types and their evolutionary origin are often unknown. Here, we study the evolution of cell differentiation in the context of surface colonization. We particularly focus on the evolution of a 'sticky' cell type that is required for surface attachment, but is costly to express. The sticky cells not only facilitate their own attachment, but also that of non-sticky cells. Using individual-based simulations, we show that surface colonization rapidly evolves and in most cases leads to phenotypic heterogeneity, in which sticky and non-sticky cells occur side by side on the surface. In the presence of regulation, cell differentiation leads to a remarkable set of bacterial life cycles, in which cells alternate between living in the liquid and living on the surface. The dominant life stage is formed by the surface-attached colony that shows many complex features: colonies reproduce via fission and by producing migratory propagules; cells inside the colony divide labour; and colonies can produce filaments to facilitate expansion. Overall, our model illustrates how the evolution of an adhesive cell type goes hand in hand with the evolution of complex bacterial life cycles.
Figueroa, Coyolxauhqui; Salazar, Gerardo A.; Zavaleta, H. Araceli; Engleman, E. Mark
2008-01-01
Background and Aims Previous studies have suggested that velamen characteristics are useful as taxonomic markers in Orchidaceae. Members of tribe Cranichideae have been assigned to two velamen types constructed based on combinations of characters such as the presence of secondary cell-wall thickenings and pores. However, such characters have not been analysed on an individual basis in explicit cladistic analyses. Methods The micromorphology of roots of 26 species of Cranichideae was examined through scanning electron microscopy and light microscopy, scoring the variation and distribution of four characters: number of velamen cell layers, velamen cell-wall thickenings, presence and type of tilosomes, and supraendodermal spaces. The last three characters were analysed cladistically in combination with DNA sequence data of plastid trnK/matK and nuclear ribosomal internal transcribed spacer (ITS) regions and optimized on the resulting phylogenetic tree. Key Results Thickenings of velamen cell walls group Prescottiinae with Spiranthinae, whereas tilosomes, documented here for the first time in Cranichideae, provide an unambiguous synapomorphy for subtribe Spiranthinae. Supraendodermal spaces occur mostly in species dwelling in seasonally dry habitats and appear to have evolved three times. Conclusions Three of the four structural characters assessed are phylogenetically informative, marking monophyletic groups recovered in the combined molecular–morphological analysis. This study highlights the need for conducting character-based structural studies to overcome analytical shortcomings of the typological approach. PMID:18263628
NASA Astrophysics Data System (ADS)
Liu, L.; Wang, S. Y.; Wang, S.; Hua, H.; Zhang, S. Q.; Meng, J.; Bark, R. A.; Wyngaardt, S. M.; Qi, B.; Sun, D. P.; Liu, C.; Li, Z. Q.; Jia, H.; Li, X. Q.; Xu, C.; Li, Z. H.; Sun, J. J.; Zhu, L. H.; Jones, P.; Lawrie, E. A.; Lawrie, J. J.; Wiedeking, M.; Bucher, T. D.; Dinoko, T.; Makhathini, L.; Majola, S. N. T.; Noncolela, S. P.; Shirinda, O.; Gál, J.; Kalinka, G.; Molnár, J.; Nyakó, B. M.; Timár, J.; Juhász, K.; Arogunjo, M.
2018-04-01
Excited states in 155Tm have been populated via the reaction 144Sm(16O, p 4 n )155Tm at a beam energy of 118 MeV. The ground-state band has been extended and a new side band of the ground-state band is identified. E-GOS curves and potential energy surface calculations are employed to discuss the structure evolution of the ground-state band. The newly observed side band in 155Tm is discussed based on the spin/energy systematics. In particular, the phenomenon of seniority inversion is proposed in 155Tm, and a systematic study of this phenomenon in the A ≈150 mass region is performed.
NASA Astrophysics Data System (ADS)
Leith, Alex P.; Ratan, Rabindra A.; Wohn, Donghee Yvette
2016-08-01
Given the diversity and complexity of education game mechanisms and topics, this article contributes to a theoretical understanding of how game mechanisms "map" to educational topics through inquiry-based learning. Namely, the article examines the presence of evolution through natural selection (ENS) in digital games. ENS is a fundamentally important and widely misunderstood theory. This analysis of ENS portrayal in digital games provides insight into the use of games in teaching ENS. Systematic database search results were coded for the three principles of ENS: phenotypic variation, differential fitness, and fitness heritability. Though thousands of games use the term evolution, few presented elements of evolution, and even fewer contained all principles of ENS. Games developed to specifically teach evolution were difficult to find through Web searches. These overall deficiencies in ENS games reflect the inherent incompatibility between game control elements and the automatic process of ENS.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Tingting; Kirchhoff, Helmut; Gargouri, Mahmoud
Mixotrophic growth of microalgae offers great potential as an efficient strategy for biofuel production. In this study, photosynthetic regulation of mixotrophically cultured Chlorella sorokiniana cells was systematically evaluated. Mixotrophic cells in the exponential growth phase showed the highest photosynthetic activity, where maximum photosynthetic O 2 evolution was approximately 3- and 4-fold higher than cells in the same phase grown photoautotrophically in 1% CO 2 (in air) and air, respectively. Additionally, characteristic chlorophyll fluorescence parameters demonstrated that no limitation in electron transport downstream of PSII was detected in mixotrophic cells. Up-regulation of photosynthetic activity was associated with high total ribulose-1, 5-bisphosphatemore » carboxylase/oxygenase (Rubisco) carboxylase activity and expression level of phosphoribulokinase (PRK). After 3 days, photosynthetic O 2 evolution of mixotrophic cells that went to the stationary phase, was strongly reduced, with reduced photochemical efficiency and reorganization of the PSII complex. Simultaneously, enzymatic activity for Rubisco carboxylase and mRNA levels of Rubisco and PRK diminished. Importantly, there was almost no non-photochemical quenching for mixotrophic cells, whether grown in log or stationary phase. A decline in the quantum efficiency of PSII and an oxidized plastoquinone pool (PQ pool) was observed under N-depleted conditions during mixotrophic growth. Finally, these results demonstrate that photosynthesis is regulated differently in mixotrophically cultured C. sorokiniana cells than in cells grown under photoautotrophic conditions, with a particularly strong impact by nitrogen levels in the cells.« less
Photo-degradation of high efficiency fullerene-free polymer solar cells.
Upama, Mushfika Baishakhi; Wright, Matthew; Mahmud, Md Arafat; Elumalai, Naveen Kumar; Mahboubi Soufiani, Arman; Wang, Dian; Xu, Cheng; Uddin, Ashraf
2017-12-07
Polymer solar cells are a promising technology for the commercialization of low cost, large scale organic solar cells. With the evolution of high efficiency (>13%) non-fullerene polymer solar cells, the stability of the cells has become a crucial parameter to be considered. Among the several degradation mechanisms of polymer solar cells, burn-in photo-degradation is relatively less studied. Herein, we present the first systematic study of photo-degradation of novel PBDB-T:ITIC fullerene-free polymer solar cells. The thermally treated and as-prepared PBDB-T:ITIC solar cells were exposed to continuous 1 sun illumination for 5 hours. The aged devices exhibited rapid losses in the short-circuit current density and fill factor. The severe short-circuit current and fill factor burn in losses were attributed to trap mediated charge recombination, as evidenced by an increase in Urbach energy for aged devices.
Kunwar, Sundar; Pandey, Puran; Sui, Mao; Zhang, Quanzhen; Li, Ming-Yu; Lee, Jihoon
2017-12-01
Si-based optoelectronic devices embedded with metallic nanoparticles (NPs) have demonstrated the NP shape, size, spacing, and crystallinity dependent on light absorption and emission induced by the localized surface plasmon resonance. In this work, we demonstrate various sizes and configurations of palladium (Pd) nanostructures on Si (111) by the systematic thermal annealing with the variation of Pd thickness and annealing temperature. The evolution of Pd nanostructures are systematically controlled by the dewetting of thin film by means of the surface diffusion in conjunction with the surface and interface energy minimization and Volmer-Weber growth model. Depending on the control of deposition amount ranging between 0.5 and 100 nm at various annealing temperatures, four distinctive regimes of Pd nanostructures are demonstrated: (i) small pits and grain formation, (ii) nucleation and growth of NPs, (iii) lateral evolution of NPs, and (iv) merged nanostructures. In addition, by the control of annealing between 300 and 800 °C, the Pd nanostructures show the evolution of small pits and grains, isolated NPs, and finally, Pd NP-assisted nanohole formation along with the Si decomposition and Pd-Si inter-diffusion. The Raman analysis showed the discrepancies on phonon modes of Si (111) such that the decreased peak intensity with left shift after the fabrication of Pd nanostructures. Furthermore, the UV-VIS-NIR reflectance spectra revealed the existence of surface morphology dependent on absorption, scattering, and reflectance properties.
NASA Astrophysics Data System (ADS)
Kunwar, Sundar; Pandey, Puran; Sui, Mao; Zhang, Quanzhen; Li, Ming-Yu; Lee, Jihoon
2017-05-01
Si-based optoelectronic devices embedded with metallic nanoparticles (NPs) have demonstrated the NP shape, size, spacing, and crystallinity dependent on light absorption and emission induced by the localized surface plasmon resonance. In this work, we demonstrate various sizes and configurations of palladium (Pd) nanostructures on Si (111) by the systematic thermal annealing with the variation of Pd thickness and annealing temperature. The evolution of Pd nanostructures are systematically controlled by the dewetting of thin film by means of the surface diffusion in conjunction with the surface and interface energy minimization and Volmer-Weber growth model. Depending on the control of deposition amount ranging between 0.5 and 100 nm at various annealing temperatures, four distinctive regimes of Pd nanostructures are demonstrated: (i) small pits and grain formation, (ii) nucleation and growth of NPs, (iii) lateral evolution of NPs, and (iv) merged nanostructures. In addition, by the control of annealing between 300 and 800 °C, the Pd nanostructures show the evolution of small pits and grains, isolated NPs, and finally, Pd NP-assisted nanohole formation along with the Si decomposition and Pd-Si inter-diffusion. The Raman analysis showed the discrepancies on phonon modes of Si (111) such that the decreased peak intensity with left shift after the fabrication of Pd nanostructures. Furthermore, the UV-VIS-NIR reflectance spectra revealed the existence of surface morphology dependent on absorption, scattering, and reflectance properties.
Lee, Cheng-Kuang; Pao, Chun-Wei
2016-08-17
Solution-processed small-molecule organic solar cells are a promising renewable energy source because of their low production cost, mechanical flexibility, and light weight relative to their pure inorganic counterparts. In this work, we developed a coarse-grained (CG) Gay-Berne ellipsoid molecular simulation model based on atomistic trajectories from all-atom molecular dynamics simulations of smaller system sizes to systematically study the nanomorphology of the SMDPPEH/PCBM/solvent ternary blend during solution processing, including the blade-coating process by applying external shear to the solution. With the significantly reduced overall system degrees of freedom and computational acceleration from GPU, we were able to go well beyond the limitation of conventional all-atom molecular simulations with a system size on the order of hundreds of nanometers with mesoscale molecular detail. Our simulations indicate that, similar to polymer solar cells, the optimal blending ratio in small-molecule organic solar cells must provide the highest specific interfacial area for efficient exciton dissociation, while retaining balanced hole/electron transport pathway percolation. We also reveal that blade-coating processes have a significant impact on nanomorphology. For given donor/acceptor blending ratios, applying an external shear force can effectively promote donor/acceptor phase segregation and stacking in the SMDPPEH domains. The present study demonstrated the capability of an ellipsoid-based coarse-grained model for studying the nanomorphology evolution of small-molecule organic solar cells during solution processing/blade-coating and provided links between fabrication protocols and device nanomorphologies.
Bickel, Balthasar; Witzlack-Makarevich, Alena; Choudhary, Kamal K; Schlesewsky, Matthias; Bornkessel-Schlesewsky, Ina
2015-01-01
Do principles of language processing in the brain affect the way grammar evolves over time or is language change just a matter of socio-historical contingency? While the balance of evidence has been ambiguous and controversial, we identify here a neurophysiological constraint on the processing of language that has a systematic effect on the evolution of how noun phrases are marked by case (i.e. by such contrasts as between the English base form she and the object form her). In neurophysiological experiments across diverse languages we found that during processing, participants initially interpret the first base-form noun phrase they hear (e.g. she…) as an agent (which would fit a continuation like … greeted him), even when the sentence later requires the interpretation of a patient role (as in … was greeted). We show that this processing principle is also operative in Hindi, a language where initial base-form noun phrases most commonly denote patients because many agents receive a special case marker ("ergative") and are often left out in discourse. This finding suggests that the principle is species-wide and independent of the structural affordances of specific languages. As such, the principle favors the development and maintenance of case-marking systems that equate base-form cases with agents rather than with patients. We confirm this evolutionary bias by statistical analyses of phylogenetic signals in over 600 languages worldwide, controlling for confounding effects from language contact. Our findings suggest that at least one core property of grammar systematically adapts in its evolution to the neurophysiological conditions of the brain, independently of socio-historical factors. This opens up new avenues for understanding how specific properties of grammar have developed in tight interaction with the biological evolution of our species.
Multiscale modeling of the dynamics of multicellular systems
NASA Astrophysics Data System (ADS)
Kosztin, Ioan
2011-03-01
Describing the biomechanical properties of cellular systems, regarded as complex highly viscoelastic materials, is a difficult problem of great conceptual and practical value. Here we present a novel approach, referred to as the Cellular Particle Dynamics (CPD) method, for: (i) quantitatively relating biomechanical properties at the cell level to those at the multicellular and tissue level, and (ii) describing and predicting the time evolution of multicellular systems that undergo biomechanical relaxations. In CPD cells are modeled as an ensemble of cellular particles (CPs) that interact via short range contact interactions, characterized by an attractive (adhesive interaction) and a repulsive (excluded volume interaction) component. The time evolution of the spatial conformation of the multicellular system is determined by following the trajectories of all CPs through integration of their equations of motion. Cell and multicellular level biomechanical properties (e.g., viscosity, surface tension and shear modulus) are determined through the combined use of experiments and theory of continuum viscoelastic media. The same biomechanical properties are also ``measured'' computationally by employing the CPD method, the results being expressed in terms of CPD parameters. Once these parameters have been calibrated experimentally, the formalism provides a systematic framework to predict the time evolution of complex multicellular systems during shape-changing biomechanical transformations. By design, the CPD method is rather flexible and most suitable for multiscale modeling of multicellular system. The spatial level of detail of the system can be easily tuned by changing the number of CPs in a cell. Thus, CPD can be used equally well to describe both cell level processes (e.g., the adhesion of two cells) and tissue level processes (e.g., the formation of 3D constructs of millions of cells through bioprinting). Work supported by NSF [FIBR-0526854 and PHY-0957914]. Computer time provided by the University of Missouri Bioinformatics Consortium.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tomar, Vikas
2017-03-06
DoE-NETL partnered with Purdue University to predict the creep and associated microstructure evolution of tungsten-based refractory alloys. Researchers use grain boundary (GB) diagrams, a new concept, to establish time-dependent creep resistance and associated microstructure evolution of grain boundaries/intergranular films GB/IGF controlled creep as a function of load, environment, and temperature. The goal was to conduct a systematic study that includes the development of a theoretical framework, multiscale modeling, and experimental validation using W-based body-centered-cubic alloys, doped/alloyed with one or two of the following elements: nickel, palladium, cobalt, iron, and copper—typical refractory alloys. Prior work has already established and validated amore » basic theory for W-based binary and ternary alloys; the study conducted under this project extended this proven work. Based on interface diagrams phase field models were developed to predict long term microstructural evolution. In order to validate the models nanoindentation creep data was used to elucidate the role played by the interface properties in predicting long term creep strength and microstructure evolution.« less
NASA Astrophysics Data System (ADS)
Kunwar, Sundar; Li, Ming-Yu; Pandey, Puran; Sui, Mao; Zhang, Quanzhen; Lee, Jihoon
2016-12-01
Silver (Ag) nanoparticles (NPs) have been widely adapted in various optoelectronic and sensing applications due to the size, shape and density dependent tunable properties. In this work, the systematic control of the size, configuration and density of self-assembled Ag nanostructures on c-plane sapphire (0001) is demonstrated through the solid state dewetting process by the variation of deposition amount (DA) at two distinctive temperature of 400 °C and 650 °C. The corresponding morphological evolution of Ag nanostructures is systematically discussed based on the diffusion, Volmer-Weber and coalescence growth model. In specific, at the relatively lower temperature of 400 °C, the Ag nanostructures evolve in three distinctive regimes based on the DA control: i.e. the dome-shaped Ag NPs between 2 and 14 nm (regime I), the irregular nano-mounds (NMs) between 20 and 40 nm (regime II), and the coalescence of Ag NMs into a layer between 60 and 200 nm (regime III). Meanwhile, at the relatively higher temperature of 650 °C, due to growth regime shift induced by the enhanced surface diffusion based on the increased thermal energy, the connected Ag NMs are resulted even at higher DAs and evolve along with the gradually increased DAs. The evolution of optical properties such as average reflectivity, plasmonic absorption band and the reflectance maxima (peaks) very sensitively respond to the evolution of size, shape and spacing of Ag nanostructures and discussed based on the surface plasmon, reflection and scattering. Specifically, the dome-shaped configuration exhibits strong absorption in the NIR region and weak absorption in visible region while the elongated NMs show the enhanced absorption in visible region. Furthermore, the Raman spectra (A 1g vibrational mode) of the Ag nanostructures demonstrate the strong correlation with the evolution of size, density and surface coverage of the nanostructures.
Phenotypic Heterogeneity and the Evolution of Bacterial Life Cycles
van Gestel, Jordi; Nowak, Martin A.
2016-01-01
Most bacteria live in colonies, where they often express different cell types. The ecological significance of these cell types and their evolutionary origin are often unknown. Here, we study the evolution of cell differentiation in the context of surface colonization. We particularly focus on the evolution of a ‘sticky’ cell type that is required for surface attachment, but is costly to express. The sticky cells not only facilitate their own attachment, but also that of non-sticky cells. Using individual-based simulations, we show that surface colonization rapidly evolves and in most cases leads to phenotypic heterogeneity, in which sticky and non-sticky cells occur side by side on the surface. In the presence of regulation, cell differentiation leads to a remarkable set of bacterial life cycles, in which cells alternate between living in the liquid and living on the surface. The dominant life stage is formed by the surface-attached colony that shows many complex features: colonies reproduce via fission and by producing migratory propagules; cells inside the colony divide labour; and colonies can produce filaments to facilitate expansion. Overall, our model illustrates how the evolution of an adhesive cell type goes hand in hand with the evolution of complex bacterial life cycles. PMID:26894881
Multi-Phase Field Models and Microstructural Evolution with Applications in Fuel Cell Technology
NASA Astrophysics Data System (ADS)
Davis, Ryan Scott
The solid oxide fuel cell (SOFC) has shown tremendous potential as an efficient energy conversion device that may be instrumental in the transition to renewable resources. However, commercialization is hindered by many degradation mechanisms that plague long term stability. In this dissertation, computation methods are used to explore the relationship between the microstructure of the fuel cell anode and performance critical metrics. The phase field method and standard modeling procedures are introduced using a classic model of spinodal decomposition. This is further developed into a complete, multi-phase modeling framework designed for the complex microstructural evolution of SOFC anode systems. High-temperature coarsening of the metallic phase in the state-of-the-art SOFC cermet anode is investigated using our phase field model. A systematic study into the effects of interface properties on microstructural evolution is accomplished by altering the contact angle between constituent phases. It is found that metrics of catalytic activity and conductivity display undesirable minima near the contact angle of conventional SOFC materials. These results suggest that tailoring the interface properties of the constituent phases could lead to a significant increase in the performance and lifetime of SOFCs. Supported-metal catalyst systems are investigated in the first detailed study of their long-term stability and application to SOFC anode design. Porous support structures are numerically sintered to mimic specific fabrication techniques, and these structures are then infiltrated with a nanoscale catalyst phase ranging from 2% to 21% loading. Initially, these systems exhibit enhanced potential for catalytic activity relative to conventional cells. However, extended evolution results in severe degradation, and we show that Ostwald ripening and particle migration are key kinetic processes. Strong geometric heterogeneity in the support structure via a novel approach to nanopore formation is proposed as a potential solution for catalyst stabilization.
Diffusion of Super-Gaussian Profiles
ERIC Educational Resources Information Center
Rosenberg, C.-J.; Anderson, D.; Desaix, M.; Johannisson, P.; Lisak, M.
2007-01-01
The present analysis describes an analytically simple and systematic approximation procedure for modelling the free diffusive spreading of initially super-Gaussian profiles. The approach is based on a self-similar ansatz for the evolution of the diffusion profile, and the parameter functions involved in the modelling are determined by suitable…
ScaleNet: A literature-based model of scale insect biology and systematics
USDA-ARS?s Scientific Manuscript database
Scale insects (Hemiptera: Coccoidea) are small herbivorous insects found in all continents except Antarctica. They are extremely invasive, and many species are serious agricultural pests. They are also emerging models for studies of the evolution of genetic systems, endosymbiosis, and plant-insect i...
Wang, Xue-Feng; Liu, Qiang; Wang, Yu-Hong; Wang, Shuai; Chen, Jie; Lin, Yue-Zhi; Ma, Jian; Zhou, Jian-Hua
2018-01-01
ABSTRACT The equine infectious anemia virus (EIAV) attenuated vaccine was developed by long-term passaging of a field-isolated virulent strain in cross-species hosts, followed by successive cultivation in cells in vitro. To explore the molecular mechanism underlying the evolution of the EIAV attenuated vaccine, a systematic study focusing on long-terminal-repeat (LTR) variation in numerous virus strains ranging from virulent EIAV to attenuated EIAV was performed over time both in vitro and in vivo. Two hypervariable regions were identified within the U3 region in the enhancer region (EHR) and the negative regulatory element (NRE) and within the R region in the transcription start site (TSS) and the Tat-activating region (TAR). Among these sites, variation in the U3 region resulted in the formation of additional transcription factor binding sites; this variation of the in vitro-adapted strains was consistent with the loss of pathogenicity. Notably, the same LTR variation pattern was observed both in vitro and in vivo. Generally, the LTR variation in both the attenuated virus and the virulent strain fluctuated over time in vivo. Interestingly, the attenuated-virus-specific LTR variation was also detected in horses infected with the virulent strain, supporting the hypothesis that the evolution of an attenuated virus might have involved branching from EIAV quasispecies. This hypothesis was verified by phylogenetic analysis. The present systematic study examining the molecular evolution of attenuated EIAV from EIAV quasispecies may provide an informative model reflecting the evolution of similar lentiviruses. IMPORTANCE The attenuated EIAV vaccine was the first lentiviral vaccine used to successfully control for equine infectious anemia in China. This vaccine provides an important reference for studying the relationship between EIAV gene variation and changes in biological characteristics. Importantly, the vaccine provides a model for the investigation of lentiviral quasispecies evolution. This study followed the “natural” development of the attenuated EIAV vaccine by use of a systematic analysis of LTR evolution in vitro and in vivo. The results revealed that the increase in LTR variation with passaging was accompanied by a decrease in virulence, which indicated that LTR variability might parallel the attenuation of virulence. Interestingly, the attenuated-virus-specific LTR variation was also detected in virulent-strain-infected horses, a finding consistent with those of previous investigations of gp90 and S2 evolution. Therefore, we present a hypothesis that the evolution of the attenuated virus may involve branching from EIAV quasispecies present in vivo. PMID:29386282
DOE Office of Scientific and Technical Information (OSTI.GOV)
Luo, Xiangyi; Amine, Rachid; Lau, Kah Chun
2017-05-26
The discharge and charge mechanisms of rechargeable Li-O-2 batteries have been the subject of extensive investigation recently. However, they are not fully understood yet. Here we report a systematic study of the morphological transition of Li2O2 from a single crystalline structure to a toroid like particle during the discharge-charge cycle, with the help of a theoretical model to explain the evolution of the Li2O2 at different stages of this process. The model suggests that the transition starts in the first monolayer of Li2O2, and is subsequently followed by a transition from particle growth to film growth if the applied currentmore » exceeds the exchange current for the oxygen reduction reaction in a Li-O-2 cell. Furthermore, a sustainable mass transport of the diffusive active species (e.g., O-2 and Li+) and evolution of the underlying interfaces are critical to dictate desirable oxygen reduction (discharge) and evolution (charge) reactions in the porous carbon electrode of a Li-O-2 cell.« less
On-chip dynamic stress control for cancer cell evolution study
NASA Astrophysics Data System (ADS)
Liu, Liyu; Austin, Robert
2010-03-01
The growth and spreading of cancer in host organisms is an evolutionary process. Cells accumulate mutations that help them adapt to changing environments and to obtain survival fitness. However, all cancer--promoting mutations do not occur at once. Cancer cells face selective environmental pressures that drive their evolution in stages. In traditional cancer studies, environmental stress is usually homogenous in space and difficult to change in time. Here, we propose a microfluidic chip employing embedded dynamic traps to generate dynamic heterogeneous microenvironments for cancer cells in evolution studies. Based on polydimethylsiloxane (PDMS) flexible diaphragms, these traps are able to enclose and shield cancer cells or expose them to external environmental stress. Digital controls for each trap determine the nutrition, antibiotics, CO2/O2 conditions, and temperatures to which trapped cells are subjected. Thus, the stress applied to cells can be varied in intensity and duration in each trap independently. The chip can also output cells from specific traps for sequencing and other biological analysis. Hence our design simultaneously monitors and analyzes cell evolution behaviors under dynamic stresses.
Aptamer-Nanoparticle Strip Biosensor for Rapid and Sensitive Detection of Cancer Cells
Mao, Xun; Phillips, Joseph A.; Xu, Hui; Tan, Weihong; Zeng, Lingwen; Liu, Guodong
2009-01-01
We report an aptamer-nanoparticle strip biosensor (ANSB) for the rapid, specific, sensitive and low-cost detection of circulating cancer cells. Known for their high specificity and affinity, aptamers were first selected from live cells by the cell-SELEX (systematic evolution of ligands by exponential enrichment) process. When next combined with the unique optical properties of gold nanoparticles (Au-NPs), ANSBs were prepared on a lateral flow device. Ramos cells were used as a model target cell to demonstrate proof of principle. Under optimal conditions, the ANSB was capable of detecting a minimum of 4000 Ramos cells without instrumentation (visual judgment) and 800 Ramos cells with a portable strip reader within 15 minutes. Importantly, ANSB has successfully detected Ramos cells in human blood, thus providing a rapid, sensitive and low-cost quantitative tool for the detection of circulating cancer cells. ANSB therefore shows great promise for in-field and point-of-care cancer diagnosis and therapy. PMID:19904989
On the thermodynamics of smooth muscle contraction
NASA Astrophysics Data System (ADS)
Stålhand, Jonas; McMeeking, Robert M.; Holzapfel, Gerhard A.
2016-09-01
Cell function is based on many dynamically complex networks of interacting biochemical reactions. Enzymes may increase the rate of only those reactions that are thermodynamically consistent. In this paper we specifically treat the contraction of smooth muscle cells from the continuum thermodynamics point of view by considering them as an open system where matter passes through the cell membrane. We systematically set up a well-known four-state kinetic model for the cross-bridge interaction of actin and myosin in smooth muscle, where the transition between each state is driven by forward and reverse reactions. Chemical, mechanical and energy balance laws are provided in local forms, while energy balance is also formulated in the more convenient temperature form. We derive the local (non-negative) production of entropy from which we deduce the reduced entropy inequality and the constitutive equations for the first Piola-Kirchhoff stress tensor, the heat flux, the ion and molecular flux and the entropy. One example for smooth muscle contraction is analyzed in more detail in order to provide orientation within the established general thermodynamic framework. In particular the stress evolution, heat generation, muscle shorting rate and a condition for muscle cooling are derived.
Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal.
Turajlic, Samra; Xu, Hang; Litchfield, Kevin; Rowan, Andrew; Horswell, Stuart; Chambers, Tim; O'Brien, Tim; Lopez, Jose I; Watkins, Thomas B K; Nicol, David; Stares, Mark; Challacombe, Ben; Hazell, Steve; Chandra, Ashish; Mitchell, Thomas J; Au, Lewis; Eichler-Jonsson, Claudia; Jabbar, Faiz; Soultati, Aspasia; Chowdhury, Simon; Rudman, Sarah; Lynch, Joanna; Fernando, Archana; Stamp, Gordon; Nye, Emma; Stewart, Aengus; Xing, Wei; Smith, Jonathan C; Escudero, Mickael; Huffman, Adam; Matthews, Nik; Elgar, Greg; Phillimore, Ben; Costa, Marta; Begum, Sharmin; Ward, Sophia; Salm, Max; Boeing, Stefan; Fisher, Rosalie; Spain, Lavinia; Navas, Carolina; Grönroos, Eva; Hobor, Sebastijan; Sharma, Sarkhara; Aurangzeb, Ismaeel; Lall, Sharanpreet; Polson, Alexander; Varia, Mary; Horsfield, Catherine; Fotiadis, Nicos; Pickering, Lisa; Schwarz, Roland F; Silva, Bruno; Herrero, Javier; Luscombe, Nick M; Jamal-Hanjani, Mariam; Rosenthal, Rachel; Birkbak, Nicolai J; Wilson, Gareth A; Pipek, Orsolya; Ribli, Dezso; Krzystanek, Marcin; Csabai, Istvan; Szallasi, Zoltan; Gore, Martin; McGranahan, Nicholas; Van Loo, Peter; Campbell, Peter; Larkin, James; Swanton, Charles
2018-04-19
The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, TRACERx Renal. We observe up to 30 driver events per tumor and show that subclonal diversification is associated with known prognostic parameters. By resolving the patterns of driver event ordering, co-occurrence, and mutual exclusivity at clone level, we show the deterministic nature of clonal evolution. ccRCC can be grouped into seven evolutionary subtypes, ranging from tumors characterized by early fixation of multiple mutational and copy number drivers and rapid metastases to highly branched tumors with >10 subclonal drivers and extensive parallel evolution associated with attenuated progression. We identify genetic diversity and chromosomal complexity as determinants of patient outcome. Our insights reconcile the variable clinical behavior of ccRCC and suggest evolutionary potential as a biomarker for both intervention and surveillance. Copyright © 2018 Francis Crick Institute. Published by Elsevier Inc. All rights reserved.
The Evolution of the Stem Cell Theory for Heart Failure.
Silvestre, Jean-Sébastien; Menasché, Philippe
2015-12-01
Various stem cell-based approaches for cardiac repair have achieved encouraging results in animal experiments, often leading to their rapid proceeding to clinical testing. However, freewheeling evolutionary developments of the stem cell theory might lead to dystopian scenarios where heterogeneous sources of therapeutic cells could promote mixed clinical outcomes in un-stratified patient populations. This review focuses on the lessons that should be learnt from the first generation of stem cell-based strategies and emphasizes the absolute requirement to better understand the basic mechanisms of stem cell biology and cardiogenesis. We will also discuss about the unexpected "big bang" in the stem cell theory, "blasting" the therapeutic cells to their unchallenged ability to release paracrine factors such as extracellular membrane vesicles. Paradoxically, the natural evolution of the stem cell theory for cardiac regeneration may end with the development of cell-free strategies with multiple cellular targets including cardiomyocytes but also other infiltrating or resident cardiac cells.
Assessment of photosynthesis regulation in mixotrophically cultured microalga Chlorella sorokiniana
Li, Tingting; Kirchhoff, Helmut; Gargouri, Mahmoud; ...
2016-07-19
Mixotrophic growth of microalgae offers great potential as an efficient strategy for biofuel production. In this study, photosynthetic regulation of mixotrophically cultured Chlorella sorokiniana cells was systematically evaluated. Mixotrophic cells in the exponential growth phase showed the highest photosynthetic activity, where maximum photosynthetic O 2 evolution was approximately 3- and 4-fold higher than cells in the same phase grown photoautotrophically in 1% CO 2 (in air) and air, respectively. Additionally, characteristic chlorophyll fluorescence parameters demonstrated that no limitation in electron transport downstream of PSII was detected in mixotrophic cells. Up-regulation of photosynthetic activity was associated with high total ribulose-1, 5-bisphosphatemore » carboxylase/oxygenase (Rubisco) carboxylase activity and expression level of phosphoribulokinase (PRK). After 3 days, photosynthetic O 2 evolution of mixotrophic cells that went to the stationary phase, was strongly reduced, with reduced photochemical efficiency and reorganization of the PSII complex. Simultaneously, enzymatic activity for Rubisco carboxylase and mRNA levels of Rubisco and PRK diminished. Importantly, there was almost no non-photochemical quenching for mixotrophic cells, whether grown in log or stationary phase. A decline in the quantum efficiency of PSII and an oxidized plastoquinone pool (PQ pool) was observed under N-depleted conditions during mixotrophic growth. Finally, these results demonstrate that photosynthesis is regulated differently in mixotrophically cultured C. sorokiniana cells than in cells grown under photoautotrophic conditions, with a particularly strong impact by nitrogen levels in the cells.« less
Alloplastic temporomandibular joint replacement systems: a systematic review of their history.
De Meurechy, N; Mommaerts, M Y
2018-06-01
This systematic review provides an overview of the historical evolution of the prosthetic temporomandibular joint and addresses the challenges and complications faced by engineers and surgeons, in an effort to shed light on why only a few systems remain available. A better understanding of the history of temporomandibular joint prostheses might also provide insights into the origin of the negative public opinion of the prosthesis, which is based on outdated information. A computerized search using the PubMed Central, ScienceDirect, Wiley Online, Ovid, and Cochrane Library databases was performed following the PRISMA guidelines. Out of 7122 articles identified, 41 met the inclusion criteria for this systematic review. Although several historical reviews have been published previously, none has covered such an extensive time period or has described all designs. Furthermore, besides providing a historical overview, this review discusses the rationale behind the evolution in design and biomaterials, which have largely contributed to the outcomes of the prosthetic systems. Copyright © 2018 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Effects of conformism on the cultural evolution of social behaviour.
Molleman, Lucas; Pen, Ido; Weissing, Franz J
2013-01-01
Models of cultural evolution study how the distribution of cultural traits changes over time. The dynamics of cultural evolution strongly depends on the way these traits are transmitted between individuals by social learning. Two prominent forms of social learning are payoff-based learning (imitating others that have higher payoffs) and conformist learning (imitating locally common behaviours). How payoff-based and conformist learning affect the cultural evolution of cooperation is currently a matter of lively debate, but few studies systematically analyse the interplay of these forms of social learning. Here we perform such a study by investigating how the interaction of payoff-based and conformist learning affects the outcome of cultural evolution in three social contexts. First, we develop a simple argument that provides insights into how the outcome of cultural evolution will change when more and more conformist learning is added to payoff-based learning. In a social dilemma (e.g. a Prisoner's Dilemma), conformism can turn cooperation into a stable equilibrium; in an evasion game (e.g. a Hawk-Dove game or a Snowdrift game) conformism tends to destabilize the polymorphic equilibrium; and in a coordination game (e.g. a Stag Hunt game), conformism changes the basin of attraction of the two equilibria. Second, we analyse a stochastic event-based model, revealing that conformism increases the speed of cultural evolution towards pure equilibria. Individual-based simulations as well as the analysis of the diffusion approximation of the stochastic model by and large confirm our findings. Third, we investigate the effect of an increasing degree of conformism on cultural group selection in a group-structured population. We conclude that, in contrast to statements in the literature, conformism hinders rather than promotes the evolution of cooperation.
Volcanic stratigraphy: A review
NASA Astrophysics Data System (ADS)
Martí, Joan; Groppelli, Gianluca; Brum da Silveira, Antonio
2018-05-01
Volcanic stratigraphy is a fundamental component of geological mapping in volcanic areas as it yields the basic criteria and essential data for identifying the spatial and temporal relationships between volcanic products and intra/inter-eruptive processes (earth-surface, tectonic and climatic), which in turn provides greater understanding of the geological evolution of a region. Establishing precise stratigraphic relationships in volcanic successions is not only essential for understanding the past behaviour of volcanoes and for predicting how they might behave in the future, but is also critical for establishing guidelines for exploring economic and energy resources associated with volcanic systems or for reconstructing the evolution of sedimentary basins in which volcanism has played a significant role. Like classical stratigraphy, volcanic stratigraphy should also be defined using a systematic methodology that can provide an organised and comprehensive description of the temporal and spatial evolution of volcanic terrain. This review explores different methods employed in studies of volcanic stratigraphy, examines four case studies that use differing stratigraphic approaches, and recommends methods for using systematic volcanic stratigraphy based on the application of the concepts of traditional stratigraphy but adapted to the needs of volcanological environment.
Zhou, Yong-Ning; Ma, Jun; Hu, Enyuan; ...
2014-11-18
Through a systematic study of lithium molybdenum trioxide (Li 2MoO 3), a new ‘unit cell breathing’ mechanism is introduced based on both crystal and electronic structural changes of transition metal oxide cathode materials during charge–discharge: For widely used LiMO 2 (M = Co, Ni, Mn), lattice parameters, a and b, contracts during charge. However, for Li 2MoO 3, such changes are in opposite directions. Metal–metal bonding is used to explain such ‘abnormal’ behaviour and a generalized hypothesis is developed. The expansion of M–M bond becomes the controlling factor for a(b) evolution during charge, in contrast to the shrinking M–O asmore » controlling factor in ‘normal’ materials. The cation mixing caused by migration of Mo ions at higher oxidation state provides the benefits of reducing the c expansion range in early stage of charging and suppressing the structure collapse at high voltage charge. These results open a new strategy for designing and engineering layered cathode materials for high energy density lithium-ion batteries.« less
A review on g-C3N4-based photocatalysts
NASA Astrophysics Data System (ADS)
Wen, Jiuqing; Xie, Jun; Chen, Xiaobo; Li, Xin
2017-01-01
As one of the most appealing and attractive technologies, heterogeneous photocatalysis has been utilized to directly harvest, convert and store renewable solar energy for producing sustainable and green solar fuels and a broad range of environmental applications. Due to their unique physicochemical, optical and electrical properties, a wide variety of g-C3N4-based photocatalysts have been designed to drive various reduction and oxidation reactions under light irradiation with suitable wavelengths. In this review, we have systematically summarized the photocatalytic fundamentals of g-C3N4-based photocatalysts, including fundamental mechanism of heterogeneous photocatalysis, advantages, challenges and the design considerations of g-C3N4-based photocatalysts. The versatile properties of g-C3N4-based photocatalysts are highlighted, including their crystal structural, surface phisicochemical, stability, optical, adsorption, electrochemical, photoelectrochemical and electronic properties. Various design strategies are also thoroughly reviewed, including band-gap engineering, defect control, dimensionality tuning, pore texture tailoring, surface sensitization, heterojunction construction, co-catalyst and nanocarbon loading. Many important applications are also addressed, such as photocatalytic water splitting (H2 evolution and overall water splitting), degradation of pollutants, carbon dioxide reduction, selective organic transformations and disinfection. Through reviewing the important state-of-the-art advances on this topic, it may provide new opportunities for designing and constructing highly effective g-C3N4-based photocatalysts for various applications in photocatalysis and other related fields, such as solar cell, photoelectrocatalysis, electrocatalysis, lithium battery, supercapacitor, fuel cell and separation and purification.
Aimaiti, Rusitanmujiang; Qin, Lianhua; Cao, Ting; Yang, Hua; Wang, Jie; Lu, Junmei; Huang, Xiaochen; Hu, Zhongyi
2015-11-01
Microscopy of direct smear with the Ziehl-Neelsen stain is still broadly used in tuberculosis diagnosis. However, this method suffers from low specificity and is difficult to distinguish Mycobacterium tuberculosis (MTB) from nontuberculosis mycobacterial (NTM), since all mycobacterial species are positive in Ziehl-Neelsen stain. In this study, we utilized whole cell SELEX to obtain species-specific aptamers for increasing the specificity of MTB detection. Whole cell SELEX was performed in MTB reference strain H37Rv by two selection processes based on enzyme-linked plate or Eppendorf tube, respectively. To increase success rate of generating aptamers, the selection processes were systematically monitored to understand the dynamic evolution of aptamers against complex structure of target bacteria. Two preponderant groups and ten high-affinity aptamers were obtained by analyzing the dynamic evolution. Preponderant aptamer MA1 from group I showed relatively high binding affinity with apparent dissociation constant (KD value) of 12.02 nM. Sandwich ELISA assay revealed five aptamer combinations effectively bound MTB strains in preliminary evaluation, especially the combination based on aptamer MA2 (another preponderant aptamer from group II) and MA1. Further evaluated in many other strains, MA2/MA1 combination effectively identified MTB from NTM or other pathogenic bacteria, and displayed the high specificity and sensitivity. Binding analysis of aptamer MA1 or MA2 by fluorescence microscopy observation showed high binding reactivity with H37Rv, low apparent cross-reactivity with M. marinum, and no apparent cross-reactivity with Enterobacter cloacae. Taken together, this study provides attractive candidate species-specific aptamers to effectively capture or discriminate MTB strains.
Genomics and Evolution in Traditional Medicinal Plants: Road to a Healthier Life
Hao, Da-Cheng; Xiao, Pei-Gen
2015-01-01
Medicinal plants have long been utilized in traditional medicine and ethnomedicine worldwide. This review presents a glimpse of the current status of and future trends in medicinal plant genomics, evolution, and phylogeny. These dynamic fields are at the intersection of phytochemistry and plant biology and are concerned with the evolution mechanisms and systematics of medicinal plant genomes, origin and evolution of the plant genotype and metabolic phenotype, interaction between medicinal plant genomes and their environment, the correlation between genomic diversity and metabolite diversity, and so on. Use of the emerging high-end genomic technologies can be expanded from crop plants to traditional medicinal plants, in order to expedite medicinal plant breeding and transform them into living factories of medicinal compounds. The utility of molecular phylogeny and phylogenomics in predicting chemodiversity and bioprospecting is also highlighted within the context of natural-product-based drug discovery and development. Representative case studies of medicinal plant genome, phylogeny, and evolution are summarized to exemplify the expansion of knowledge pedigree and the paradigm shift to the omics-based approaches, which update our awareness about plant genome evolution and enable the molecular breeding of medicinal plants and the sustainable utilization of plant pharmaceutical resources. PMID:26461812
Genomics and Evolution in Traditional Medicinal Plants: Road to a Healthier Life.
Hao, Da-Cheng; Xiao, Pei-Gen
2015-01-01
Medicinal plants have long been utilized in traditional medicine and ethnomedicine worldwide. This review presents a glimpse of the current status of and future trends in medicinal plant genomics, evolution, and phylogeny. These dynamic fields are at the intersection of phytochemistry and plant biology and are concerned with the evolution mechanisms and systematics of medicinal plant genomes, origin and evolution of the plant genotype and metabolic phenotype, interaction between medicinal plant genomes and their environment, the correlation between genomic diversity and metabolite diversity, and so on. Use of the emerging high-end genomic technologies can be expanded from crop plants to traditional medicinal plants, in order to expedite medicinal plant breeding and transform them into living factories of medicinal compounds. The utility of molecular phylogeny and phylogenomics in predicting chemodiversity and bioprospecting is also highlighted within the context of natural-product-based drug discovery and development. Representative case studies of medicinal plant genome, phylogeny, and evolution are summarized to exemplify the expansion of knowledge pedigree and the paradigm shift to the omics-based approaches, which update our awareness about plant genome evolution and enable the molecular breeding of medicinal plants and the sustainable utilization of plant pharmaceutical resources.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Zhangwei; Baker, Ian; Cai, Zhonghou
2016-11-01
A systematic study of the effects of up to 1.1 at. % carbon on the mechanical properties and evolution of the dislocation substructure in a series of a high entropy alloys (HEA) based on Fe40.4Ni11.3Mn34.8Al7.5Cr6 is presented. Transmission electron microscopy (TEM), synchrotron X-ray diffraction (XRD) and atom probe tomography (APT) were used to show that all the alloys are single-phase f.c.c. random solid solutions. The lattice constant, determined from synchrotron XRD measurements, increases linearly with increasing carbon concentration, which leads to a linear relationship between the yield strength and the carbon concentration. The dislocation substructures, as determined by a TEM,more » show a transition from wavy slip to planar slip and, at higher strains, and from cell-forming structure (dislocations cells, cell blocks and dense dislocation walls) to non-cell forming structure (Taylor lattice, microbands and domain boundaries) with the addition of carbon, features related to the increase in lattice friction stress. The stacking fault energy (measured via weak-beam imaging of the separation of dislocation partials) decreases with increasing carbon content, which also contributes to the transition from wavy slip to planar slip. The formation of non-cell forming structure induced by carbon leads to a high degree of strain hardening and a substantial increase in the ultimate tensile strength. The consequent postponement of necking due to the high strain hardening, along with the plasticity accommodation arising from the formation of microbands and domain boundaries, result in an increase of ductility due to the carbon addition. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.« less
Microorganism and filamentous fungi drive evolution of plant synapses.
Baluška, František; Mancuso, Stefano
2013-01-01
In the course of plant evolution, there is an obvious trend toward an increased complexity of plant bodies, as well as an increased sophistication of plant behavior and communication. Phenotypic plasticity of plants is based on the polar auxin transport machinery that is directly linked with plant sensory systems impinging on plant behavior and adaptive responses. Similar to the emergence and evolution of eukaryotic cells, evolution of land plants was also shaped and driven by infective and symbiotic microorganisms. These microorganisms are the driving force behind the evolution of plant synapses and other neuronal aspects of higher plants; this is especially pronounced in the root apices. Plant synapses allow synaptic cell-cell communication and coordination in plants, as well as sensory-motor integration in root apices searching for water and mineral nutrition. These neuronal aspects of higher plants are closely linked with their unique ability to adapt to environmental changes.
Evolution of the Air Toxics under the Big Sky Program
ERIC Educational Resources Information Center
Marra, Nancy; Vanek, Diana; Hester, Carolyn; Holian, Andrij; Ward, Tony; Adams, Earle; Knuth, Randy
2011-01-01
As a yearlong exploration of air quality and its relation to respiratory health, the "Air Toxics Under the Big Sky" program offers opportunities for students to learn and apply science process skills through self-designed inquiry-based research projects conducted within their communities. The program follows a systematic scope and sequence…
Does Tumor Development Follow a Programmed Path?
NASA Astrophysics Data System (ADS)
Austin, Robert
2011-03-01
The initiation and progression of a tumor is a complex process, resembling the growth of a embryo in terms of the stages of development and increasing differentiation and somatic evolution of constituent cells in the community of cells that constitute the tumor. Typically we view cancer cells as rogue individuals violating the rules of the games played within an organism, but I would suggest that what we see is a programmed and algorithmic process. I will then question If tumor progression is dominated by the random acquisition of successive survival traits, or by a systematic and sequential unpacking of ``weapons'' from a pre-adapted ``toolkit'' of genetic and epigenetic potentialities? Can we then address this hypothesis by data mining solid tumors layer by layer? Support of the NSF and the NCI is gratefully acknowledged.
Kinetoplastid phylogenetics, with special reference to the evolution of parasitic trypanosomes.
Stevens, J R
2008-09-01
To fully understand the evolutionary history of parasitic kinetoplastids and to understand the context within which the evolution of each parasite group has developed, an understanding not just of the parasites, but of all kinetoplastids is required. Accordingly, this paper provides an overview of kinetoplastid evolution and systematics, including coverage of the proposal by Moreira et al. (2004) to divide kinetoplasts into Prokinetoplastina (Ichthyobodo and Perkinsiella) and Metakinetoplastina (other bodonids and trypanosomatids). The implications of such a revision, with regard to correctly identifying outgroup taxa for studies of evolution within taxa of medical importance, are addressed, together with a more detailed review of the evolution and origins of the trypanosomes in the light of new phylogenies, new approaches and revisions in kinetoplastid systematics.
Effects of oxygen partial pressure on Li-air battery performance
NASA Astrophysics Data System (ADS)
Kwon, Hyuk Jae; Lee, Heung Chan; Ko, Jeongsik; Jung, In Sun; Lee, Hyun Chul; Lee, Hyunpyo; Kim, Mokwon; Lee, Dong Joon; Kim, Hyunjin; Kim, Tae Young; Im, Dongmin
2017-10-01
For application in electric vehicles (EVs), the Li-air battery system needs an air intake system to supply dry oxygen at controlled concentration and feeding rate as the cathode active material. To facilitate the design of such air intake systems, we have investigated the effects of oxygen partial pressure (≤1 atm) on the performance of the Li-air cell, which has not been systematically examined. The amounts of consumed O2 and evolved CO2 from the Li-air cell are measured with a custom in situ differential electrochemical gas chromatography-mass spectrometry (DEGC-MS). The amounts of consumed O2 suggest that the oxygen partial pressure does not affect the reaction mechanism during discharge, and the two-electron reaction occurs under all test conditions. On the other hand, the charging behavior varies by the oxygen partial pressure. The highest O2 evolution ratio is attained under 70% O2, along with the lowest CO2 evolution. The cell cycle life also peaks at 70% O2 condition. Overall, an oxygen partial pressure of about 0.5-0.7 atm maximizes the Li-air cell capacity and stability at 1 atm condition. The findings here indicate that the appropriate oxygen partial pressure can be a key factor when developing practical Li-air battery systems.
NASA Astrophysics Data System (ADS)
Chadel, Meriem; Moustafa Bouzaki, Mohammed; Chadel, Asma; Aillerie, Michel; Benyoucef, Boumediene
2017-07-01
The influence of the thickness of a Zinc Oxide (ZnO) transparent conductive oxide (TCO) layer on the performance of the CZTSSe solar cell is shown in detail. In a photovoltaic cell, the thickness of each layer largely influence the performance of the solar cell and optimization of each layer constitutes a complete work. Here, using the Solar Cell Capacitance Simulation (SCAPS) software, we present simulation results obtained in the analyze of the influence of the TCO layer thickness on the performance of a CZTSSe solar cell, starting from performance of a CZTSSe solar cell commercialized in 2014 with an initial efficiency equal to 12.6%. In simulation, the temperature was considered as a functioning parameter and the evolution of tthe performance of the cell for various thickness of the TCO layer when the external temperature changes is simulated and discussed. The best efficiency of the solar cell based in CZTSSe is obtained with a ZnO thickness equal to 50 nm and low temperature. Based on the considered marketed cell, we show a technological possible increase of the global efficiency achieving 13% by optimization of ZnO based TCO layer.
Huang, Shengfeng; Yuan, Shaochun; Dong, Meiling; Su, Jing; Yu, Cuiling; Shen, Yang; Xie, Xiaojin; Yu, Yanhong; Yu, Xuesong; Chen, Shangwu; Zhang, Shicui; Pontarotti, Pierre; Xu, Anlong
2005-12-01
In animals, the tetraspanins are a large superfamily of membrane proteins that play important roles in organizing various cell-cell and matrix-cell interactions and signal pathways based on such interactions. However, their origin and evolution largely remain elusive and most of the family's members are functionally unknown or less known due to difficulties of study, such as functional redundancy. In this study, we rebuilt the family's phylogeny with sequences retrieved from online databases and our cDNA library of amphioxus. We reveal that, in addition to in metazoans, various tetraspanins are extensively expressed in protozoan amoebae, fungi, and plants. We also discuss the structural evolution of tetraspanin's major extracellular domain and the relation between tetraspanin's duplication and functional redundancy. Finally, we elucidate the coevolution of tetraspanins and eukaryotes and suggest that tetraspanins play important roles in the unicell-to-multicell transition. In short, the study of tetraspanin in a phylogenetic context helps us understand the evolution of intercellular interactions.
The physical characteristics of human proteins in different biological functions.
Wang, Tengjiao; Tang, Hailin
2017-01-01
The physical properties of gene products are the foundation of their biological functions. In this study, we systematically explored relationships between physical properties and biological functions. The physical properties including origin time, evolution pressure, mRNA and protein stability, molecular weight, hydrophobicity, acidity/alkaline, amino acid compositions, and chromosome location. The biological functions are defined from 4 aspects: biological process, molecular function, cellular component and cell/tissue/organ expression. We found that the proteins associated with basic material and energy metabolism process originated earlier, while the proteins associated with immune, neurological system process etc. originated later. Tissues may have a strong influence on evolution pressure. The proteins associated with energy metabolism are double-stable. Immune and peripheral cell proteins tend to be mRNA stable/protein unstable. There are very few function items with double-unstable of mRNA and protein. The proteins involved in the cell adhesion tend to consist of large proteins with high proportion of small amino acids. The proteins of organic acid transport, neurological system process and amine transport have significantly high hydrophobicity. Interestingly, the proteins involved in olfactory receptor activity tend to have high frequency of aromatic, sulfuric and hydroxyl amino acids.
The physical characteristics of human proteins in different biological functions
Tang, Hailin
2017-01-01
The physical properties of gene products are the foundation of their biological functions. In this study, we systematically explored relationships between physical properties and biological functions. The physical properties including origin time, evolution pressure, mRNA and protein stability, molecular weight, hydrophobicity, acidity/alkaline, amino acid compositions, and chromosome location. The biological functions are defined from 4 aspects: biological process, molecular function, cellular component and cell/tissue/organ expression. We found that the proteins associated with basic material and energy metabolism process originated earlier, while the proteins associated with immune, neurological system process etc. originated later. Tissues may have a strong influence on evolution pressure. The proteins associated with energy metabolism are double-stable. Immune and peripheral cell proteins tend to be mRNA stable/protein unstable. There are very few function items with double-unstable of mRNA and protein. The proteins involved in the cell adhesion tend to consist of large proteins with high proportion of small amino acids. The proteins of organic acid transport, neurological system process and amine transport have significantly high hydrophobicity. Interestingly, the proteins involved in olfactory receptor activity tend to have high frequency of aromatic, sulfuric and hydroxyl amino acids. PMID:28459865
Diversity-Oriented Synthesis as a Strategy for Fragment Evolution against GSK3β.
Wang, Yikai; Wach, Jean-Yves; Sheehan, Patrick; Zhong, Cheng; Zhan, Chenyang; Harris, Richard; Almo, Steven C; Bishop, Joshua; Haggarty, Stephen J; Ramek, Alexander; Berry, Kayla N; O'Herin, Conor; Koehler, Angela N; Hung, Alvin W; Young, Damian W
2016-09-08
Traditional fragment-based drug discovery (FBDD) relies heavily on structural analysis of the hits bound to their targets. Herein, we present a complementary approach based on diversity-oriented synthesis (DOS). A DOS-based fragment collection was able to produce initial hit compounds against the target GSK3β, allow the systematic synthesis of related fragment analogues to explore fragment-level structure-activity relationship, and finally lead to the synthesis of a more potent compound.
NASA Astrophysics Data System (ADS)
Mursula, K.; Virtanen, I.
2012-04-01
We reanalyze the observations of the heliospheric magnetic field (HMF) made by the Pioneer 10 and 11 and Voyager 1 and 2 heliospheric probes since 1972, and calculate the HMF sector occurrence ratios and tangential component strengths in the different regions of the heliosphere. Observations at the distant probes and at 1 AU show a very consistent picture of the HMF sector structure in the entire heliosphere, and even beyond the termination shock. Pioneer 11 and Voyager 1 show that the development of northern polar coronal holes was very systematic and active during all the four solar minima since mid-1970s. On the other hand, Voyager 2 observations show a less systematic and delayed development of southern coronal holes in 1980s, 1990s and 2000s. This delay in the evolution of southern coronal holes with respect to the rapid and systematic evolution of northern coronal holes leads to a larger extent of northern coronal holes and a southward shift of the heliospheric current sheet (the bashful ballerina phenomenon) for a few years in the late declining phase of each solar cycle. HMF observations of the probes also directly verify the HCS southward shift, supporting earlier observations at 1-2 AU by the Ulysses probe and Earth-orbiting satellites and extending them into the more distant heliosphere. Although the evidence for the connection between the temporal difference in the evolution of polar coronal holes and the bashful ballerina times is based only on three solar cycles, this may be a common pattern for solar coronal hole evolution since the southward shift of the HCS has occurred at least since solar cycle 16.
The Evolution of the Stem Cell Theory for Heart Failure
Silvestre, Jean-Sébastien; Menasché, Philippe
2015-01-01
Various stem cell-based approaches for cardiac repair have achieved encouraging results in animal experiments, often leading to their rapid proceeding to clinical testing. However, freewheeling evolutionary developments of the stem cell theory might lead to dystopian scenarios where heterogeneous sources of therapeutic cells could promote mixed clinical outcomes in un-stratified patient populations. This review focuses on the lessons that should be learnt from the first generation of stem cell-based strategies and emphasizes the absolute requirement to better understand the basic mechanisms of stem cell biology and cardiogenesis. We will also discuss about the unexpected “big bang” in the stem cell theory, “blasting” the therapeutic cells to their unchallenged ability to release paracrine factors such as extracellular membrane vesicles. Paradoxically, the natural evolution of the stem cell theory for cardiac regeneration may end with the development of cell-free strategies with multiple cellular targets including cardiomyocytes but also other infiltrating or resident cardiac cells. PMID:26844266
Polymer Electrolyte Membranes for Water Photo-Electrolysis
Aricò, Antonino S.; Girolamo, Mariarita; Siracusano, Stefania; Sebastian, David; Baglio, Vincenzo; Schuster, Michael
2017-01-01
Water-fed photo-electrolysis cells equipped with perfluorosulfonic acid (Nafion® 115) and quaternary ammonium-based (Fumatech® FAA3) ion exchange membranes as separator for hydrogen and oxygen evolution reactions were investigated. Protonic or anionic ionomer dispersions were deposited on the electrodes to extend the interface with the electrolyte. The photo-anode consisted of a large band-gap Ti-oxide semiconductor. The effect of membrane characteristics on the photo-electrochemical conversion of solar energy was investigated for photo-voltage-driven electrolysis cells. Photo-electrolysis cells were also studied for operation under electrical bias-assisted mode. The pH of the membrane/ionomer had a paramount effect on the photo-electrolytic conversion. The anionic membrane showed enhanced performance compared to the Nafion®-based cell when just TiO2 anatase was used as photo-anode. This was associated with better oxygen evolution kinetics in alkaline conditions compared to acidic environment. However, oxygen evolution kinetics in acidic conditions were significantly enhanced by using a Ti sub-oxide as surface promoter in order to facilitate the adsorption of OH species as precursors of oxygen evolution. However, the same surface promoter appeared to inhibit oxygen evolution in an alkaline environment probably as a consequence of the strong adsorption of OH species on the surface under such conditions. These results show that a proper combination of photo-anode and polymer electrolyte membrane is essential to maximize photo-electrolytic conversion. PMID:28468242
Polymer Electrolyte Membranes for Water Photo-Electrolysis.
Aricò, Antonino S; Girolamo, Mariarita; Siracusano, Stefania; Sebastian, David; Baglio, Vincenzo; Schuster, Michael
2017-04-29
Water-fed photo-electrolysis cells equipped with perfluorosulfonic acid (Nafion ® 115) and quaternary ammonium-based (Fumatech ® FAA3) ion exchange membranes as separator for hydrogen and oxygen evolution reactions were investigated. Protonic or anionic ionomer dispersions were deposited on the electrodes to extend the interface with the electrolyte. The photo-anode consisted of a large band-gap Ti-oxide semiconductor. The effect of membrane characteristics on the photo-electrochemical conversion of solar energy was investigated for photo-voltage-driven electrolysis cells. Photo-electrolysis cells were also studied for operation under electrical bias-assisted mode. The pH of the membrane/ionomer had a paramount effect on the photo-electrolytic conversion. The anionic membrane showed enhanced performance compared to the Nafion ® -based cell when just TiO₂ anatase was used as photo-anode. This was associated with better oxygen evolution kinetics in alkaline conditions compared to acidic environment. However, oxygen evolution kinetics in acidic conditions were significantly enhanced by using a Ti sub-oxide as surface promoter in order to facilitate the adsorption of OH species as precursors of oxygen evolution. However, the same surface promoter appeared to inhibit oxygen evolution in an alkaline environment probably as a consequence of the strong adsorption of OH species on the surface under such conditions. These results show that a proper combination of photo-anode and polymer electrolyte membrane is essential to maximize photo-electrolytic conversion.
Nickel-based anodic electrocatalysts for fuel cells and water splitting
NASA Astrophysics Data System (ADS)
Chen, Dayi
Our world is facing an energy crisis, so people are trying to harvest and utilize energy more efficiently. One of the promising ways to harvest energy is via solar water splitting to convert solar energy to chemical energy stored in hydrogen. Another of the options to utilize energy more efficiently is to use fuel cells as power sources instead of combustion engines. Catalysts are needed to reduce the energy barriers of the reactions happening at the electrode surfaces of the water-splitting cells and fuel cells. Nickel-based catalysts happen to be important nonprecious electrocatalysts for both of the anodic reactions in alkaline media. In alcohol fuel cells, nickel-based catalysts catalyze alcohol oxidation. In water splitting cells, they catalyze water oxidation, i.e., oxygen evolution. The two reactions occur in a similar potential range when catalyzed by nickel-based catalysts. Higher output current density, lower oxidation potential, and complete substrate oxidation are preferred for the anode in the applications. In this dissertation, the catalytic properties of nickel-based electrocatalysts in alkaline medium for fuel oxidation and oxygen evolution are explored. By changing the nickel precursor solubility, nickel complex nanoparticles with tunable sizes on electrode surfaces were synthesized. Higher methanol oxidation current density is achieved with smaller nickel complex nanoparticles. DNA aggregates were used as a polymer scaffold to load nickel ion centers and thus can oxidize methanol completely at a potential about 0.1 V lower than simple nickel electrodes, and the methanol oxidation pathway is changed. Nickel-based catalysts also have electrocatalytic activity towards a wide range of substrates. Experiments show that methanol, ethanol, glycerol and glucose can be deeply oxidized and carbon-carbon bonds can be broken during the oxidation. However, when comparing methanol oxidation reaction to oxygen evolution reaction catalyzed by current nickel-based catalysts, methanol oxidation suffers from high overpotential and catalyst poisoning by high concentration of substrates, so current nickel-based catalysts are more suitable to be used as oxygen evolution catalysts. A photoanode design that applies nickel oxides to a semiconductor that is incorporated with surface-plasmonic metal electrodes to do solar water oxidation with visible light is proposed.
Negotiation of intracellular membrane barriers by TAT-modified gold nanoparticles.
Krpetić, Zeljka; Saleemi, Samia; Prior, Ian A; Sée, Violaine; Qureshi, Rumana; Brust, Mathias
2011-06-28
This paper contributes to the debate on how nanosized objects negotiate membrane barriers inside biological cells. The uptake of peptide-modified gold nanoparticles by HeLa cells has been quantified using atomic emission spectroscopy. The TAT peptide from the HIV virus was singled out as a particularly effective promoter of cellular uptake. The evolution of the intracellular distribution of TAT-modified gold nanoparticles with time has been studied in detail by TEM and systematic image analysis. An unusual trend of particles disappearing from the cytosol and the nucleus and accumulating massively in vesicular bodies was observed. Subsequent release of the particles, both by membrane rupture and by direct transfer across the membrane boundary, was frequently found. Ultimately, near total clearing of particles from the cells occurred. This work provides support for the hypothesis that cell-penetrating peptides can enable small objects to negotiate membrane barriers also in the absence of dedicated transport mechanisms.
Man-made Boards Technology Trends based on TRIZ Evolution Theory
NASA Astrophysics Data System (ADS)
Yu, Huiling; Fan, Delin
China is one of the world's largest manufacturers and consumers of man-made board applications. A systematic and efficient method of foreseeing future technology trends and their evolutionary potentials is a key task that can help companies guide their planning and allocate their resources. Application of the law of evolution with a S-shaped curve could contribute essentially to the accuracy of the long-term forecast. This research seeks to determine the current stage and the position on the S-curve of man-made board technology in China on the TRIZ evolution theo ryand introduce a methodology which combines patent analysis and technology life cycle forecasting to find a niche space of man-made technology development in China.
NASA Astrophysics Data System (ADS)
Chen, Xinxian; Tan, Zhenyu; Liu, Yadi; Li, Xiaotong; Pan, Jie; Wang, Xiaolong
2017-08-01
This work presents a systematical investigation on the spatiotemporal evolution of the energy spectrum of electrons in atmospheric pressure argon plasma jets and its dependence on the applied voltage. The investigations are carried out by means of the numerical simulation based on a particle-in-cell Monte-Carlo collision model. The characteristics of the spatiotemporal evolution of the energy spectrum of electrons (ESE) in the discharge space have been presented, and especially the mechanisms of inducing these characteristics have also been revealed. The present work shows the following conclusions. In the evolution of ESE, there is a characteristic time under each applied voltage. Before the characteristic time, the peak value of ESE decreases, the peak position shifts toward high energy, and the distribution of ESE becomes wider and wider, but the reverse is true after the characteristic time. The formation of these characteristics can be mainly attributed to the transport of electrons toward a low electric field as well as a balance between the energy gained from the electric field including the effect of space charges and the energy loss due to inelastic collisions in the process of electron transport. The characteristic time decreases with the applied voltage. In addition, the average energy of electrons at the characteristic time can be increased by enhancing the applied voltage. The results presented in this work are of importance for regulating and controlling the energy of electrons in the plasma jets applied to plasma medicine.
Accelerated and Adaptive Evolution of Yeast Sexual Adhesins
Xie, Xianfa; Qiu, Wei-Gang; Lipke, Peter N.
2011-01-01
There is a recent emergence of interest in the genes involved in gametic recognition as drivers of reproductive isolation. The recent population genomic sequencing of two species of sexually primitive yeasts (Liti G, Carter DM, Moses AM, Warringer J, Parts L, James SA, Davey RP, Roberts IN, Burt A, Koufopanou V et al. [23 co-authors]. 2009. Population genomics of domestic and wild yeasts. Nature 458:337–341.) has provided data for systematic study of the roles these genes play in the early evolution of sex and speciation. Here, we discovered that among genes encoding cell surface proteins, the sexual adhesin genes have evolved significantly more rapidly than others, both within and between Saccharomyces cerevisiae and its closest relative S. paradoxus. This result was supported by analyses using the PAML pairwise model, a modified McDonald–Kreitman test, and the PAML branch model. Moreover, using a combination of a new statistic of neutrality, an information theory–based measure of evolutionary variability, and functional characterization of amino acid changes, we found that a higher proportion of amino acid changes are fixed in the sexual adhesins than in other proteins and a greater proportion of the fixed amino acid changes either between the two species or the two subgroups of S. paradoxus are functionally dissimilar or radically different. These results suggest that the accelerated evolution of sexual adhesin genes may facilitate speciation, or incipient speciation, and promote sexual selection in general. PMID:21633112
Storyboarding: A Method for Bootstrapping the Design of Computer-Based Educational Tasks
ERIC Educational Resources Information Center
Jones, Ian
2008-01-01
There has been a recent call for the use of more systematic thought experiments when investigating learning. This paper presents a storyboarding method for capturing and sharing initial ideas and their evolution in the design of a mathematics learning task. The storyboards produced can be considered as "virtual data" created by thought experiments…
Diversity-Oriented Synthesis as a Strategy for Fragment Evolution against GSK3β
2016-01-01
Traditional fragment-based drug discovery (FBDD) relies heavily on structural analysis of the hits bound to their targets. Herein, we present a complementary approach based on diversity-oriented synthesis (DOS). A DOS-based fragment collection was able to produce initial hit compounds against the target GSK3β, allow the systematic synthesis of related fragment analogues to explore fragment-level structure–activity relationship, and finally lead to the synthesis of a more potent compound. PMID:27660690
Wang, Maojun; Yuan, Daojun; Gao, Wenhui; Li, Yang; Tan, Jiafu; Zhang, Xianlong
2013-01-01
Pectins are fundamental polysaccharides in the plant primary cell wall. Pectins are synthesized and secreted to cell walls as highly methyl-esterified polymers and then demethyl-esterified by pectin methylesterases (PMEs), which are spatially regulated by pectin methylesterase inhibitors (PMEIs). Although PME and PMEI genes are pivotal in plant cell wall formation, few studies have focused on the evolutionary patterns of the PME and PMEI gene families. In this study, the gene origin, evolution, and expression diversity of these two families were systematically analyzed using 11 representative species, including algae, bryophytes, lycophytes and flowering land plants. The results show that 1) for the two subfamilies (PME and proPME) of PME, the origin of the PME subfamily is consistent with the appearance of pectins in early charophyte cell walls, 2) Whole genome duplication (WGD) and tandem duplication contribute to the expansion of proPME and PMEI families in land plants, 3) Evidence of selection pressure shows that the proPME and PMEI families have rapidly evolved, particularly the PMEI family in vascular plants, and 4) Comparative expression profile analysis of the two families indicates that the eudicot Arabidopsis and monocot rice have different expression patterns. In addition, the gene structure and sequence analyses show that the origin of the PMEI domain may be derived from the neofunctionalization of the pro domain after WGD. This study will advance the evolutionary understanding of the PME and PMEI families and plant cell wall development.
Cancer evolution: mathematical models and computational inference.
Beerenwinkel, Niko; Schwarz, Roland F; Gerstung, Moritz; Markowetz, Florian
2015-01-01
Cancer is a somatic evolutionary process characterized by the accumulation of mutations, which contribute to tumor growth, clinical progression, immune escape, and drug resistance development. Evolutionary theory can be used to analyze the dynamics of tumor cell populations and to make inference about the evolutionary history of a tumor from molecular data. We review recent approaches to modeling the evolution of cancer, including population dynamics models of tumor initiation and progression, phylogenetic methods to model the evolutionary relationship between tumor subclones, and probabilistic graphical models to describe dependencies among mutations. Evolutionary modeling helps to understand how tumors arise and will also play an increasingly important prognostic role in predicting disease progression and the outcome of medical interventions, such as targeted therapy. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society of Systematic Biologists.
Antibiotic combination efficacy (ACE) networks for a Pseudomonas aeruginosa model
Barbosa, Camilo; Beardmore, Robert; Jansen, Gunther
2018-01-01
The spread of antibiotic resistance is always a consequence of evolutionary processes. The consideration of evolution is thus key to the development of sustainable therapy. Two main factors were recently proposed to enhance long-term effectiveness of drug combinations: evolved collateral sensitivities between the drugs in a pair and antagonistic drug interactions. We systematically assessed these factors by performing over 1,600 evolution experiments with the opportunistic nosocomial pathogen Pseudomonas aeruginosa in single- and multidrug environments. Based on the growth dynamics during these experiments, we reconstructed antibiotic combination efficacy (ACE) networks as a new tool for characterizing the ability of the tested drug combinations to constrain bacterial survival as well as drug resistance evolution across time. Subsequent statistical analysis of the influence of the factors on ACE network characteristics revealed that (i) synergistic drug interactions increased the likelihood of bacterial population extinction—irrespective of whether combinations were compared at the same level of inhibition or not—while (ii) the potential for evolved collateral sensitivities between 2 drugs accounted for a reduction in bacterial adaptation rates. In sum, our systematic experimental analysis allowed us to pinpoint 2 complementary determinants of combination efficacy and to identify specific drug pairs with high ACE scores. Our findings can guide attempts to further improve the sustainability of antibiotic therapy by simultaneously reducing pathogen load and resistance evolution. PMID:29708964
Wu, Zeng-Yuan; Milne, Richard I.; Chen, Chia-Jui; Liu, Jie; Wang, Hong; Li, De-Zhu
2015-01-01
Urticaceae is a family with more than 2000 species, which contains remarkable morphological diversity. It has undergone many taxonomic reorganizations, and is currently the subject of further systematic studies. To gain more resolution in systematic studies and to better understand the general patterns of character evolution in Urticaceae, based on our previous phylogeny including 169 accessions comprising 122 species across 47 Urticaceae genera, we examined 19 diagnostic characters, and analysed these employing both maximum-parsimony and maximum-likelihood approaches. Our results revealed that 16 characters exhibited multiple state changes within the family, with ten exhibiting >eight changes and three exhibiting between 28 and 40. Morphological synapomorphies were identified for many clades, but the diagnostic value of these was often limited due to reversals within the clade and/or homoplasies elsewhere. Recognition of the four clades comprising the family at subfamily level can be supported by a small number carefully chosen defining traits for each. Several non-monophyletic genera appear to be defined only by characters that are plesiomorphic within their clades, and more detailed work would be valuable to find defining traits for monophyletic clades within these. Some character evolution may be attributed to adaptive evolution in Urticaceae due to shifts in habitat or vegetation type. This study demonstrated the value of using phylogeny to trace character evolution, and determine the relative importance of morphological traits for classification. PMID:26529598
DOE Office of Scientific and Technical Information (OSTI.GOV)
Verhertbruggen, Yves; Walker, Jesse L.; Guillon, Fabienne
Staining and immunodetection by light microscopy are methods widely used to investigate plant cell walls. The two techniques have been crucial to study the cell wall architecture in planta, its deconstruction by chemicals or cell wall-degrading enzymes. They have been instrumental in detecting the presence of cell types, in deciphering plant cell wall evolution and in characterizing plant mutants and transformants. The success of immunolabeling relies on how plant materials are embedded and sectioned. Agarose coating, wax and resin embedding are, respectively, associated with vibratome, microtome and ultramicrotome sectioning. Here, we have systematically carried out a comparative analysis of thesemore » three methods of sample preparation when they are applied for cell wall staining and cell wall immunomicroscopy. In order to help the plant community in understanding and selecting adequate methods of embedding and sectioning for cell wall immunodetection, we review in this article the advantages and limitations of these three methods. Moreover, we offer detailed protocols of embedding for studying plant materials through microscopy.« less
Verhertbruggen, Yves; Walker, Jesse L.; Guillon, Fabienne; ...
2017-08-29
Staining and immunodetection by light microscopy are methods widely used to investigate plant cell walls. The two techniques have been crucial to study the cell wall architecture in planta, its deconstruction by chemicals or cell wall-degrading enzymes. They have been instrumental in detecting the presence of cell types, in deciphering plant cell wall evolution and in characterizing plant mutants and transformants. The success of immunolabeling relies on how plant materials are embedded and sectioned. Agarose coating, wax and resin embedding are, respectively, associated with vibratome, microtome and ultramicrotome sectioning. Here, we have systematically carried out a comparative analysis of thesemore » three methods of sample preparation when they are applied for cell wall staining and cell wall immunomicroscopy. In order to help the plant community in understanding and selecting adequate methods of embedding and sectioning for cell wall immunodetection, we review in this article the advantages and limitations of these three methods. Moreover, we offer detailed protocols of embedding for studying plant materials through microscopy.« less
Verhertbruggen, Yves; Walker, Jesse L.; Guillon, Fabienne; Scheller, Henrik V.
2017-01-01
Staining and immunodetection by light microscopy are methods widely used to investigate plant cell walls. The two techniques have been crucial to study the cell wall architecture in planta, its deconstruction by chemicals or cell wall-degrading enzymes. They have been instrumental in detecting the presence of cell types, in deciphering plant cell wall evolution and in characterizing plant mutants and transformants. The success of immunolabeling relies on how plant materials are embedded and sectioned. Agarose coating, wax and resin embedding are, respectively, associated with vibratome, microtome and ultramicrotome sectioning. Here, we have systematically carried out a comparative analysis of these three methods of sample preparation when they are applied for cell wall staining and cell wall immunomicroscopy. In order to help the plant community in understanding and selecting adequate methods of embedding and sectioning for cell wall immunodetection, we review in this article the advantages and limitations of these three methods. Moreover, we offer detailed protocols of embedding for studying plant materials through microscopy. PMID:28900439
Gardner, Shea Nicole
2007-10-23
A method and system for tailoring treatment regimens to individual patients with diseased cells exhibiting evolution of resistance to such treatments. A mathematical model is provided which models rates of population change of proliferating and quiescent diseased cells using cell kinetics and evolution of resistance of the diseased cells, and pharmacokinetic and pharmacodynamic models. Cell kinetic parameters are obtained from an individual patient and applied to the mathematical model to solve for a plurality of treatment regimens, each having a quantitative efficacy value associated therewith. A treatment regimen may then be selected from the plurlaity of treatment options based on the efficacy value.
Evolution of rational vaccine designs for genital herpes immunotherapy.
Kaufmann, Johanna Katharina; Flechtner, Jessica Baker
2016-04-01
Immunotherapeutic vaccines have emerged as a novel treatment modality for genital herpes, a sexually transmitted disease mainly caused by herpes simplex virus type 2. The approaches to identify potential vaccine antigens have evolved from classic virus attenuation and characterization of antibody and T cell responses in exposed, but seronegative individuals, to systematic screens for novel T cell antigens. Combined with implementation of novel vaccine concepts revolving around immune evasion and local recruitment of immune effectors, the development of a safe and effective therapeutic vaccine is within reach. Here, we describe the vaccine approaches that currently show promise at clinical and pre-clinical stages and link them to the evolving scientific strategies that led to their identification. Copyright © 2016 Elsevier B.V. All rights reserved.
An Improved Binary Differential Evolution Algorithm to Infer Tumor Phylogenetic Trees.
Liang, Ying; Liao, Bo; Zhu, Wen
2017-01-01
Tumourigenesis is a mutation accumulation process, which is likely to start with a mutated founder cell. The evolutionary nature of tumor development makes phylogenetic models suitable for inferring tumor evolution through genetic variation data. Copy number variation (CNV) is the major genetic marker of the genome with more genes, disease loci, and functional elements involved. Fluorescence in situ hybridization (FISH) accurately measures multiple gene copy number of hundreds of single cells. We propose an improved binary differential evolution algorithm, BDEP, to infer tumor phylogenetic tree based on FISH platform. The topology analysis of tumor progression tree shows that the pathway of tumor subcell expansion varies greatly during different stages of tumor formation. And the classification experiment shows that tree-based features are better than data-based features in distinguishing tumor. The constructed phylogenetic trees have great performance in characterizing tumor development process, which outperforms other similar algorithms.
The Teaching of Evolution--We Need To Do Better.
ERIC Educational Resources Information Center
Linhart, Yan B.
1997-01-01
Analyzes 50 major textbooks in the fields of evolution, biology, ecology, genetics, paleontology, and systematics, focusing on how the conceptual framework of evolution as a process is presented and developed in those fields. Lists definitions of evolution provided in the textbooks and discusses the implications of the findings. Contains 56…
In vitro flow cytometry-based screening platform for cellulase engineering
Körfer, Georgette; Pitzler, Christian; Vojcic, Ljubica; Martinez, Ronny; Schwaneberg, Ulrich
2016-01-01
Ultrahigh throughput screening (uHTS) plays an essential role in directed evolution for tailoring biocatalysts for industrial applications. Flow cytometry-based uHTS provides an efficient coverage of the generated protein sequence space by analysis of up to 107 events per hour. Cell-free enzyme production overcomes the challenge of diversity loss during the transformation of mutant libraries into expression hosts, enables directed evolution of toxic enzymes, and holds the promise to efficiently design enzymes of human or animal origin. The developed uHTS cell-free compartmentalization platform (InVitroFlow) is the first report in which a flow cytometry-based screened system has been combined with compartmentalized cell-free expression for directed cellulase enzyme evolution. InVitroFlow was validated by screening of a random cellulase mutant library employing a novel screening system (based on the substrate fluorescein-di-β-D-cellobioside), and yielded significantly improved cellulase variants (e.g. CelA2-H288F-M1 (N273D/H288F/N468S) with 13.3-fold increased specific activity (220.60 U/mg) compared to CelA2 wildtype: 16.57 U/mg). PMID:27184298
Volume regulation and shape bifurcation in the cell nucleus
Kim, Dong-Hwee; Li, Bo; Si, Fangwei; Phillip, Jude M.; Wirtz, Denis; Sun, Sean X.
2015-01-01
ABSTRACT Alterations in nuclear morphology are closely associated with essential cell functions, such as cell motility and polarization, and correlate with a wide range of human diseases, including cancer, muscular dystrophy, dilated cardiomyopathy and progeria. However, the mechanics and forces that shape the nucleus are not well understood. Here, we demonstrate that when an adherent cell is detached from its substratum, the nucleus undergoes a large volumetric reduction accompanied by a morphological transition from an almost smooth to a heavily folded surface. We develop a mathematical model that systematically analyzes the evolution of nuclear shape and volume. The analysis suggests that the pressure difference across the nuclear envelope, which is influenced by changes in cell volume and regulated by microtubules and actin filaments, is a major factor determining nuclear morphology. Our results show that physical and chemical properties of the extracellular microenvironment directly influence nuclear morphology and suggest that there is a direct link between the environment and gene regulation. PMID:26243474
Volume regulation and shape bifurcation in the cell nucleus.
Kim, Dong-Hwee; Li, Bo; Si, Fangwei; Phillip, Jude M; Wirtz, Denis; Sun, Sean X
2015-09-15
Alterations in nuclear morphology are closely associated with essential cell functions, such as cell motility and polarization, and correlate with a wide range of human diseases, including cancer, muscular dystrophy, dilated cardiomyopathy and progeria. However, the mechanics and forces that shape the nucleus are not well understood. Here, we demonstrate that when an adherent cell is detached from its substratum, the nucleus undergoes a large volumetric reduction accompanied by a morphological transition from an almost smooth to a heavily folded surface. We develop a mathematical model that systematically analyzes the evolution of nuclear shape and volume. The analysis suggests that the pressure difference across the nuclear envelope, which is influenced by changes in cell volume and regulated by microtubules and actin filaments, is a major factor determining nuclear morphology. Our results show that physical and chemical properties of the extracellular microenvironment directly influence nuclear morphology and suggest that there is a direct link between the environment and gene regulation. © 2015. Published by The Company of Biologists Ltd.
From sMOOC to tMOOC, Learning towards Professional Transference: ECO European Project
ERIC Educational Resources Information Center
Osuna-Acedo, Sara; Marta-Lazo, Carmen; Frau-Meigs, Divina
2018-01-01
The evolution of MOOCs in the last decade has been constant and dynamic. The first cMOOC and xMOOC models eventually evolved into different post-MOOC modalities, such as sMOOC, which conjugates interaction among students with a participation model based on social networks. This work is focused on carrying out a systematic review of the…
Shapiro, James A
2016-06-08
The 21st century genomics-based analysis of evolutionary variation reveals a number of novel features impossible to predict when Dobzhansky and other evolutionary biologists formulated the neo-Darwinian Modern Synthesis in the middle of the last century. These include three distinct realms of cell evolution; symbiogenetic fusions forming eukaryotic cells with multiple genome compartments; horizontal organelle, virus and DNA transfers; functional organization of proteins as systems of interacting domains subject to rapid evolution by exon shuffling and exonization; distributed genome networks integrated by mobile repetitive regulatory signals; and regulation of multicellular development by non-coding lncRNAs containing repetitive sequence components. Rather than single gene traits, all phenotypes involve coordinated activity by multiple interacting cell molecules. Genomes contain abundant and functional repetitive components in addition to the unique coding sequences envisaged in the early days of molecular biology. Combinatorial coding, plus the biochemical abilities cells possess to rearrange DNA molecules, constitute a powerful toolbox for adaptive genome rewriting. That is, cells possess "Read-Write Genomes" they alter by numerous biochemical processes capable of rapidly restructuring cellular DNA molecules. Rather than viewing genome evolution as a series of accidental modifications, we can now study it as a complex biological process of active self-modification.
Shapiro, James A.
2016-01-01
The 21st century genomics-based analysis of evolutionary variation reveals a number of novel features impossible to predict when Dobzhansky and other evolutionary biologists formulated the neo-Darwinian Modern Synthesis in the middle of the last century. These include three distinct realms of cell evolution; symbiogenetic fusions forming eukaryotic cells with multiple genome compartments; horizontal organelle, virus and DNA transfers; functional organization of proteins as systems of interacting domains subject to rapid evolution by exon shuffling and exonization; distributed genome networks integrated by mobile repetitive regulatory signals; and regulation of multicellular development by non-coding lncRNAs containing repetitive sequence components. Rather than single gene traits, all phenotypes involve coordinated activity by multiple interacting cell molecules. Genomes contain abundant and functional repetitive components in addition to the unique coding sequences envisaged in the early days of molecular biology. Combinatorial coding, plus the biochemical abilities cells possess to rearrange DNA molecules, constitute a powerful toolbox for adaptive genome rewriting. That is, cells possess “Read–Write Genomes” they alter by numerous biochemical processes capable of rapidly restructuring cellular DNA molecules. Rather than viewing genome evolution as a series of accidental modifications, we can now study it as a complex biological process of active self-modification. PMID:27338490
The Evolution of Human Cells in Terms of Protein Innovation
Sardar, Adam J.; Oates, Matt E.; Fang, Hai; Forrest, Alistair R.R.; Kawaji, Hideya; Gough, Julian; Rackham, Owen J.L.
2014-01-01
Humans are composed of hundreds of cell types. As the genomic DNA of each somatic cell is identical, cell type is determined by what is expressed and when. Until recently, little has been reported about the determinants of human cell identity, particularly from the joint perspective of gene evolution and expression. Here, we chart the evolutionary past of all documented human cell types via the collective histories of proteins, the principal product of gene expression. FANTOM5 data provide cell-type–specific digital expression of human protein-coding genes and the SUPERFAMILY resource is used to provide protein domain annotation. The evolutionary epoch in which each protein was created is inferred by comparison with domain annotation of all other completely sequenced genomes. Studying the distribution across epochs of genes expressed in each cell type reveals insights into human cellular evolution in terms of protein innovation. For each cell type, its history of protein innovation is charted based on the genes it expresses. Combining the histories of all cell types enables us to create a timeline of cell evolution. This timeline identifies the possibility that our common ancestor Coelomata (cavity-forming animals) provided the innovation required for the innate immune system, whereas cells which now form the brain of human have followed a trajectory of continually accumulating novel proteins since Opisthokonta (boundary of animals and fungi). We conclude that exaptation of existing domain architectures into new contexts is the dominant source of cell-type–specific domain architectures. PMID:24692656
Yang, Ming; Peng, Zhihui; Ning, Yi; Chen, Yongzhe; Zhou, Qin; Deng, Le
2013-05-22
In this paper, a panel of single-stranded DNA aptamers with high affinity and specificity against Salmonella Paratyphi A was selected from an enriched oligonucleotide pool by a whole-cell-Systematic Evolution of Ligands by Exponential Enrichment (SELEX) procedure, during which four other Salmonella serovars were used as counter-selection targets. It was determined through a fluorescence assay that the selected aptamers had high binding ability and specificity to this pathogen. The dissociation constant of these aptamers were up to nanomolar range, and aptamer Apt22 with the lowest Kd (47 ± 3 nM) was used in cell imaging experiments. To detect this bacteria with high specificity and cost-efficiently, a novel useful detection method was also constructed based on the noncovalent self-assembly of single-walled carbon nanotubes (SWNTs) and DNAzyme-labeled aptamer detection probes. The amounts of target bacteria could be quantified by exploiting chemoluminescence intensity changes at 420 nm and the detection limit of the method was 103 cfu/mL. This study demonstrated the applicability of Salmonella specific aptamers and their potential for use in the detection of Salmonella in food, clinical and environmental samples.
Danielsson, Frida; Wiking, Mikaela; Mahdessian, Diana; Skogs, Marie; Ait Blal, Hammou; Hjelmare, Martin; Stadler, Charlotte; Uhlén, Mathias; Lundberg, Emma
2013-01-04
One of the major challenges of a chromosome-centric proteome project is to explore in a systematic manner the potential proteins identified from the chromosomal genome sequence, but not yet characterized on a protein level. Here, we describe the use of RNA deep sequencing to screen human cell lines for RNA profiles and to use this information to select cell lines suitable for characterization of the corresponding gene product. In this manner, the subcellular localization of proteins can be analyzed systematically using antibody-based confocal microscopy. We demonstrate the usefulness of selecting cell lines with high expression levels of RNA transcripts to increase the likelihood of high quality immunofluorescence staining and subsequent successful subcellular localization of the corresponding protein. The results show a path to combine transcriptomics with affinity proteomics to characterize the proteins in a gene- or chromosome-centric manner.
Solving the Puzzle of Metastasis: The Evolution of Cell Migration in Neoplasms
Chen, Jun; Sprouffske, Kathleen; Huang, Qihong; Maley, Carlo C.
2011-01-01
Background Metastasis represents one of the most clinically important transitions in neoplastic progression. The evolution of metastasis is a puzzle because a metastatic clone is at a disadvantage in competition for space and resources with non-metastatic clones in the primary tumor. Metastatic clones waste some of their reproductive potential on emigrating cells with little chance of establishing metastases. We suggest that resource heterogeneity within primary tumors selects for cell migration, and that cell emigration is a by-product of that selection. Methods and Findings We developed an agent-based model to simulate the evolution of neoplastic cell migration. We simulated the essential dynamics of neoangiogenesis and blood vessel occlusion that lead to resource heterogeneity in neoplasms. We observed the probability and speed of cell migration that evolves with changes in parameters that control the degree of spatial and temporal resource heterogeneity. Across a broad range of realistic parameter values, increasing degrees of spatial and temporal heterogeneity select for the evolution of increased cell migration and emigration. Conclusions We showed that variability in resources within a neoplasm (e.g. oxygen and nutrients provided by angiogenesis) is sufficient to select for cells with high motility. These cells are also more likely to emigrate from the tumor, which is the first step in metastasis and the key to the puzzle of metastasis. Thus, we have identified a novel potential solution to the puzzle of metastasis. PMID:21556134
Recurrent genomic instability of chromosome 1q in neural derivatives of human embryonic stem cells
Varela, Christine; Denis, Jérôme Alexandre; Polentes, Jérôme; Feyeux, Maxime; Aubert, Sophie; Champon, Benoite; Piétu, Geneviève; Peschanski, Marc; Lefort, Nathalie
2012-01-01
Human pluripotent stem cells offer a limitless source of cells for regenerative medicine. Neural derivatives of human embryonic stem cells (hESCs) are currently being used for cell therapy in 3 clinical trials. However, hESCs are prone to genomic instability, which could limit their clinical utility. Here, we report that neural differentiation of hESCs systematically produced a neural stem cell population that could be propagated for more than 50 passages without entering senescence; this was true for all 6 hESC lines tested. The apparent spontaneous loss of evolution toward normal senescence of somatic cells was associated with a jumping translocation of chromosome 1q. This chromosomal defect has previously been associated with hematologic malignancies and pediatric brain tumors with poor clinical outcome. Neural stem cells carrying the 1q defect implanted into the brains of rats failed to integrate and expand, whereas normal cells engrafted. Our results call for additional quality controls to be implemented to ensure genomic integrity not only of undifferentiated pluripotent stem cells, but also of hESC derivatives that form cell therapy end products, particularly neural lines. PMID:22269325
Development of a panel of DNA Aptamers with High Affinity for Pancreatic Ductal Adenocarcinoma
Champanhac, Carole; Teng, I-Ting; Cansiz, Sena; Zhang, Liqin; Wu, Xiaoqiu; Zhoa, Zilong; Fu, Ting; Tan, Weihong
2015-01-01
Pancreatic cancer costs nearly 40,000 lives in the U.S. each year and has one of the lowest survival rates among cancers. Effective treatment of pancreatic ductal adenocarcinoma is hindered by lack of a reliable biomarker. To address this challenge, aptamers were selected by cell-SELEX (Systematic Evolution of Ligands by EXponential enrichment) targeting human pancreatic ductal adenocarcinoma (PL45). Five promising aptamers presenting low Kd values and good specificity were generated. Among these five aptamers, one was tailored into a nanostructure carrying a high drug payload for specific drug delivery. The results show a viability of almost 80% for negative cells while only 50% of the target cells remained alive after 48 h incubation. These results lead to the conclusion that further research could reveal protein biomarkers specific to pancreatic adenocarcinoma, with probes available for early detection. PMID:26603187
Development of a panel of DNA Aptamers with High Affinity for Pancreatic Ductal Adenocarcinoma
NASA Astrophysics Data System (ADS)
Champanhac, Carole; Teng, I.-Ting; Cansiz, Sena; Zhang, Liqin; Wu, Xiaoqiu; Zhoa, Zilong; Fu, Ting; Tan, Weihong
2015-11-01
Pancreatic cancer costs nearly 40,000 lives in the U.S. each year and has one of the lowest survival rates among cancers. Effective treatment of pancreatic ductal adenocarcinoma is hindered by lack of a reliable biomarker. To address this challenge, aptamers were selected by cell-SELEX (Systematic Evolution of Ligands by EXponential enrichment) targeting human pancreatic ductal adenocarcinoma (PL45). Five promising aptamers presenting low Kd values and good specificity were generated. Among these five aptamers, one was tailored into a nanostructure carrying a high drug payload for specific drug delivery. The results show a viability of almost 80% for negative cells while only 50% of the target cells remained alive after 48 h incubation. These results lead to the conclusion that further research could reveal protein biomarkers specific to pancreatic adenocarcinoma, with probes available for early detection.
Sensing Cell-Culture Assays with Low-Cost Circuitry.
Pérez, Pablo; Huertas, Gloria; Maldonado-Jacobi, Andrés; Martín, María; Serrano, Juan A; Olmo, Alberto; Daza, Paula; Yúfera, Alberto
2018-06-11
An alternative approach for cell-culture end-point protocols is proposed herein. This new technique is suitable for real-time remote sensing. It is based on Electrical Cell-substrate Impedance Spectroscopy (ECIS) and employs the Oscillation-Based Test (OBT) method. Simple and straightforward circuit blocks form the basis of the proposed measurement system. Oscillation parameters - frequency and amplitude - constitute the outcome, directly correlated with the culture status. A user can remotely track the evolution of cell cultures in real time over the complete experiment through a web tool continuously displaying the acquired data. Experiments carried out with commercial electrodes and a well-established cell line (AA8) are described, obtaining the cell number in real time from growth assays. The electrodes have been electrically characterized along the design flow in order to predict the system performance and the sensitivity curves. Curves for 1-week cell growth are reported. The obtained experimental results validate the proposed OBT for cell-culture characterization. Furthermore, the proposed electrode model provides a good approximation for the cell number and the time evolution of the studied cultures.
Kassaye, Seble; Johnston, Elizabeth; McColgan, Bryan; Kantor, Rami; Zijenah, Lynn; Katzenstein, David
2009-01-01
In resource-constrained settings, antiretroviral treatment (ART) is often continued based on clinical and CD4 responses, without virologic monitoring. ART with incomplete viral suppression was assessed in 27 subjects with subtype C HIV-1 by measuring plasma HIV-1 RNA, drug resistance, viral tropism, and evolution in polymerase (pol) and envelope (env) genes. The association between these viral parameters and CD4 cell change over time was analyzed using linear regression models. Increased area under the curve of HIV-1 RNA replication was a predictor of lower CD4 cell gains (p <0.007), while less drug resistance measured as a genotypic susceptibility score (GSS) (p=0.065), and lower rates of evolution in pol and env genes (p= 0.08 and 0.097, respectively) measured as genetic distance were modestly associated with increasing CD4 cell counts. Evolution of pol and env were correlated (R2 = 0.48, p=0.005), however, greater evolution was identified in env vs. pol (p <0.05). CXCR4-usage (X4) was detected in 14/27 (52%) but no differences in CD4 cell change or plasma viremia were associated with X4-usage. Among subtype C HIV-1 infected patients in Zimbabwe receiving incompletely suppressive ART, higher virus replication and lower CD4 cell gains were associated with drug resistance and evolution of polymerase and envelope. PMID:19295330
Student Visual Communication of Evolution
ERIC Educational Resources Information Center
Oliveira, Alandeom W.; Cook, Kristin
2017-01-01
Despite growing recognition of the importance of visual representations to science education, previous research has given attention mostly to verbal modalities of evolution instruction. Visual aspects of classroom learning of evolution are yet to be systematically examined by science educators. The present study attends to this issue by exploring…
NASA Astrophysics Data System (ADS)
Chela-Flores, Julian
1998-04-01
Our present understanding of the origin and evolution of chromosomes differs considerably from current understanding of the origin and evolution of the cell itself. Chromosome origins have been less prominent in research, as the emphasis has not shifted so far appreciably from the phenomenon of primeval nucleic acid encapsulation to that of the origin of gene organization, expression, and regulation. In this work we discuss some reasons why preliminary steps in this direction are being taken. We have been led to examine properties that have contributed to raise the ancestral prokaryotic programmes to a level where we can appreciate in eukaryotes a clear departure from earlier themes in the evolution of the cell from the last common ancestor. We shift our point of view from evolution of cell morphology to the point of view of the genes. In particular, we focus attention on possible physical bases for the way transmission of information has evolved in eukaryotes, namely, the inactivation of whole chromosomes. The special case of the inactivation of the X chromosome in mammals is discussed, paying particular attention to the physical process of the spread of X inactivation in monotremes (platypus and echidna). When experimental data is unavailable some theoretical analysis is possible based on the idea that in certain cases collective phenomena in genetics, rather than chemical detail, are better correlates of complex chemical processes.
AnnoLnc: a web server for systematically annotating novel human lncRNAs.
Hou, Mei; Tang, Xing; Tian, Feng; Shi, Fangyuan; Liu, Fenglin; Gao, Ge
2016-11-16
Long noncoding RNAs (lncRNAs) have been shown to play essential roles in almost every important biological process through multiple mechanisms. Although the repertoire of human lncRNAs has rapidly expanded, their biological function and regulation remain largely elusive, calling for a systematic and integrative annotation tool. Here we present AnnoLnc ( http://annolnc.cbi.pku.edu.cn ), a one-stop portal for systematically annotating novel human lncRNAs. Based on more than 700 data sources and various tool chains, AnnoLnc enables a systematic annotation covering genomic location, secondary structure, expression patterns, transcriptional regulation, miRNA interaction, protein interaction, genetic association and evolution. An intuitive web interface is available for interactive analysis through both desktops and mobile devices, and programmers can further integrate AnnoLnc into their pipeline through standard JSON-based Web Service APIs. To the best of our knowledge, AnnoLnc is the only web server to provide on-the-fly and systematic annotation for newly identified human lncRNAs. Compared with similar tools, the annotation generated by AnnoLnc covers a much wider spectrum with intuitive visualization. Case studies demonstrate the power of AnnoLnc in not only rediscovering known functions of human lncRNAs but also inspiring novel hypotheses.
NASA Astrophysics Data System (ADS)
Li, Zheng-Yan; Xie, Zheng-Wei; Chen, Tong; Ouyang, Qi
2009-12-01
Constraint-based models such as flux balance analysis (FBA) are a powerful tool to study biological metabolic networks. Under the hypothesis that cells operate at an optimal growth rate as the result of evolution and natural selection, this model successfully predicts most cellular behaviours in growth rate. However, the model ignores the fact that cells can change their cellular metabolic states during evolution, leaving optimal metabolic states unstable. Here, we consider all the cellular processes that change metabolic states into a single term 'noise', and assume that cells change metabolic states by randomly walking in feasible solution space. By simulating a state of a cell randomly walking in the constrained solution space of metabolic networks, we found that in a noisy environment cells in optimal states tend to travel away from these points. On considering the competition between the noise effect and the growth effect in cell evolution, we found that there exists a trade-off between these two effects. As a result, the population of the cells contains different cellular metabolic states, and the population growth rate is at suboptimal states.
Wittig-Blaich, Stephanie; Wittig, Rainer; Schmidt, Steffen; Lyer, Stefan; Bewerunge-Hudler, Melanie; Gronert-Sum, Sabine; Strobel-Freidekind, Olga; Müller, Carolin; List, Markus; Jaskot, Aleksandra; Christiansen, Helle; Hafner, Mathias; Schadendorf, Dirk; Block, Ines; Mollenhauer, Jan
2017-01-01
Next-generation sequencing has dramatically increased genome-wide profiling options and conceptually initiates the possibility for personalized cancer therapy. State-of-the-art sequencing studies yield large candidate gene sets comprising dozens or hundreds of mutated genes. However, few technologies are available for the systematic downstream evaluation of these results to identify novel starting points of future cancer therapies. We improved and extended a site-specific recombination-based system for systematic analysis of the individual functions of a large number of candidate genes. This was facilitated by a novel system for the construction of isogenic constitutive and inducible gain- and loss-of-function cell lines. Additionally, we demonstrate the construction of isogenic cell lines with combinations of the traits for advanced functional in vitro analyses. In a proof-of-concept experiment, a library of 108 isogenic melanoma cell lines was constructed and 8 genes were identified that significantly reduced viability in a discovery screen and in an independent validation screen. Here, we demonstrate the broad applicability of this recombination-based method and we proved its potential to identify new drug targets via the identification of the tumor suppressor DUSP6 as potential synthetic lethal target in melanoma cell lines with BRAF V600E mutations and high DUSP6 expression. PMID:28423600
Development of Cell-SELEX Technology and Its Application in Cancer Diagnosis and Therapy.
Chen, Man; Yu, Yuanyuan; Jiang, Feng; Zhou, Junwei; Li, Yongshu; Liang, Chao; Dang, Lei; Lu, Aiping; Zhang, Ge
2016-12-10
SELEX (systematic evolution of ligands by exponential enrichment) is a process involving the progressive isolation of high selective ssDNA/RNA from a combinatorial single-stranded oligonucleotide library through repeated rounds of binding, partitioning and amplification. SELEX-derived single-stranded DNA/RNA molecules, called aptamers, are selected against a wide range of targets, including purified proteins, live cells, tissues, microorganisms, small molecules and so on. With the development of SELEX technology over the last two decades, various modified SELEX processes have been arisen. A majority of aptamers are selected against purified proteins through traditional SELEX. Unfortunately, more and more evidence showed aptamers selected against purified membrane proteins failed to recognize their targets in live cells. Cell-SELEX could develop aptamers against a particular target cell line to discriminate this cell line from others. Therefore, cell-SELEX has been widely used to select aptamers for the application of both diagnosis and therapy of various diseases, especially for cancer. In this review, the advantages and limitations of cell-SELEX and SELEX against purified protein will be compared. Various modified cell-SELEX techniques will be summarized, and application of cell-SELEX in cancer diagnosis and therapy will be discussed.
Development of Cell-SELEX Technology and Its Application in Cancer Diagnosis and Therapy
Chen, Man; Yu, Yuanyuan; Jiang, Feng; Zhou, Junwei; Li, Yongshu; Liang, Chao; Dang, Lei; Lu, Aiping; Zhang, Ge
2016-01-01
SELEX (systematic evolution of ligands by exponential enrichment) is a process involving the progressive isolation of high selective ssDNA/RNA from a combinatorial single-stranded oligonucleotide library through repeated rounds of binding, partitioning and amplification. SELEX-derived single-stranded DNA/RNA molecules, called aptamers, are selected against a wide range of targets, including purified proteins, live cells, tissues, microorganisms, small molecules and so on. With the development of SELEX technology over the last two decades, various modified SELEX processes have been arisen. A majority of aptamers are selected against purified proteins through traditional SELEX. Unfortunately, more and more evidence showed aptamers selected against purified membrane proteins failed to recognize their targets in live cells. Cell-SELEX could develop aptamers against a particular target cell line to discriminate this cell line from others. Therefore, cell-SELEX has been widely used to select aptamers for the application of both diagnosis and therapy of various diseases, especially for cancer. In this review, the advantages and limitations of cell-SELEX and SELEX against purified protein will be compared. Various modified cell-SELEX techniques will be summarized, and application of cell-SELEX in cancer diagnosis and therapy will be discussed. PMID:27973403
Evolution of the Mauthner axon cap.
Bierman, Hilary S; Zottoli, Steven J; Hale, Melina E
2009-01-01
Studies of vertebrate brain evolution have focused primarily on patterns of gene expression or changes in size and organization of major brain regions. The Mauthner cell, an important reticulospinal neuron that functions in the startle response of many species, provides an opportunity for evolutionary comparisons at the cellular level. Despite broad interspecific similarities in Mauthner cell morphology, the motor patterns and startle behaviors it initiates vary markedly. Response diversity has been hypothesized to result, in part, from differences in the structure and function of the Mauthner cell-associated axon cap. We used light microscopy techniques to compare axon cap morphology across a wide range of species, including all four extant basal actinopterygian orders, representatives of a variety of teleost lineages and lungfishes, and we combined our data with published descriptions of axon cap structure. The 'composite' axon cap, observed in teleosts, is an organized conglomeration of glia and fibers of inhibitory and excitatory interneurons. Lungfish, amphibian tadpoles and several basal actinopterygian fishes have 'simple' axon caps that appear to lack glia and include few fibers. Several other basal actinopterygian fishes have 'simple-dense' caps that include greater numbers of fibers than simple caps, but lack the additional elements and organization of composite caps. Phylogenetic mapping shows that through evolution there are discrete transitions in axon cap morphology occurring at the base of gnathostomes, within basal actinopterygians, and at the base of the teleost radiation. Comparing axon cap evolution to the evolution of startle behavior and motor pattern provides insight into the relationship between Mauthner cell-associated structures and their functions in behavior. Copyright 2009 S. Karger AG, Basel.
Systematic Applications of Metabolomics in Metabolic Engineering
Dromms, Robert A.; Styczynski, Mark P.
2012-01-01
The goals of metabolic engineering are well-served by the biological information provided by metabolomics: information on how the cell is currently using its biochemical resources is perhaps one of the best ways to inform strategies to engineer a cell to produce a target compound. Using the analysis of extracellular or intracellular levels of the target compound (or a few closely related molecules) to drive metabolic engineering is quite common. However, there is surprisingly little systematic use of metabolomics datasets, which simultaneously measure hundreds of metabolites rather than just a few, for that same purpose. Here, we review the most common systematic approaches to integrating metabolite data with metabolic engineering, with emphasis on existing efforts to use whole-metabolome datasets. We then review some of the most common approaches for computational modeling of cell-wide metabolism, including constraint-based models, and discuss current computational approaches that explicitly use metabolomics data. We conclude with discussion of the broader potential of computational approaches that systematically use metabolomics data to drive metabolic engineering. PMID:24957776
NASA Astrophysics Data System (ADS)
Sui, Mao; Li, Ming-Yu; Pandey, Puran; Zhang, Quanzhen; Kunwar, Sundar; Lee, Jihoon
2018-03-01
Owing to their tunable properties, Ag nanostructures have been widely adapted in various applications and the morphological control can determine their performance and effectiveness. In this work, we demonstrate the morphological and optical evolution of Ag nanostructures on GaN (0001) by the systematic control of deposition amount at two distinctive annealing temperatures. Based on the Volmer-Weber and coalescence growth models, the nanostructure growth commenced by the thermal solid-state-dewetting evolve in terms of size, density and configuration. At 450 °C, the round-dome shaped Ag nanoparticles (regime I), irregular Ag nano-mounds (regime II) and void-layer structures (regime III) are observed along with the gradually increased deposition amount. As a sharp distinction, the solid state dewetting process occur more radically at 700 °C and also, the Ag sublimation and the effect on the nanostructure formation are observed in a clear regime shift scaled by the deposition amount. Meanwhile, a strong dependency of reflectance spectra evolution on the Ag nanostructure morphology is witnessed for both sets. In particular, Ag dipolar resonance peaks are significantly red-shifted from VIS to NIR regions along with the nanostructure evolution. The reflectance, PL and Raman intensity variation are also observed and discussed based on the evolution of Ag nanostructures.
Microorganism and filamentous fungi drive evolution of plant synapses
Baluška, František; Mancuso, Stefano
2013-01-01
In the course of plant evolution, there is an obvious trend toward an increased complexity of plant bodies, as well as an increased sophistication of plant behavior and communication. Phenotypic plasticity of plants is based on the polar auxin transport machinery that is directly linked with plant sensory systems impinging on plant behavior and adaptive responses. Similar to the emergence and evolution of eukaryotic cells, evolution of land plants was also shaped and driven by infective and symbiotic microorganisms. These microorganisms are the driving force behind the evolution of plant synapses and other neuronal aspects of higher plants; this is especially pronounced in the root apices. Plant synapses allow synaptic cell–cell communication and coordination in plants, as well as sensory-motor integration in root apices searching for water and mineral nutrition. These neuronal aspects of higher plants are closely linked with their unique ability to adapt to environmental changes. PMID:23967407
Role of strain and conductivity in oxygen electrocatalysis on LaCoO3 thin films
Stoerzinger, Kelsey; Choi, Woo Seok; Jeen, Hyoung Jeen; ...
2015-01-19
The slow kinetics of the oxygen reduction and evolution reactions (ORR, OER) hinder energy conversion and storage in alkaline fuel cells and electrolyzers employing abundant transition metal oxide catalysts. Systematic studies linking material properties to catalytic activity are lacking, in part due to the heterogeneous nature of powder-based electrodes. We demonstrate, for the first time, that epitaxial strain can tune the activity of oxygen electrocatalysis in alkaline solutions, focusing on the model chemistry of LaCoO 3, where moderate tensile strain can further induce changes in the electronic structure via spin state to increase activity. The resultant decrease in charge transfermore » resistance to the electrolyte reduces the overpotential in the ORR more notably than the OER and suggests a different dependence of the respective rate-limiting steps on electron transfer. This provides new insight into the reaction mechanism applicable to a range of perovskite chemistries, key to the rational design of highly active catalysts.« less
Generation of structurally novel short carotenoids and study of their biological activity
Kim, Se H.; Kim, Moon S.; Lee, Bun Y.; Lee, Pyung C.
2016-01-01
Recent research interest in phytochemicals has consistently driven the efforts in the metabolic engineering field toward microbial production of various carotenoids. In spite of systematic studies, the possibility of using C30 carotenoids as biologically functional compounds has not been explored thus far. Here, we generated 13 novel structures of C30 carotenoids and one C35 carotenoid, including acyclic, monocyclic, and bicyclic structures, through directed evolution and combinatorial biosynthesis, in Escherichia coli. Measurement of radical scavenging activity of various C30 carotenoid structures revealed that acyclic C30 carotenoids showed higher radical scavenging activity than did DL-α-tocopherol. We could assume high potential biological activity of the novel structures of C30 carotenoids as well, based on the neuronal differentiation activity observed for the monocyclic C30 carotenoid 4,4′-diapotorulene on rat bone marrow mesenchymal stem cells. Our results demonstrate that a series of structurally novel carotenoids possessing biologically beneficial properties can be synthesized in E. coli. PMID:26902326
Generation of structurally novel short carotenoids and study of their biological activity.
Kim, Se H; Kim, Moon S; Lee, Bun Y; Lee, Pyung C
2016-02-23
Recent research interest in phytochemicals has consistently driven the efforts in the metabolic engineering field toward microbial production of various carotenoids. In spite of systematic studies, the possibility of using C30 carotenoids as biologically functional compounds has not been explored thus far. Here, we generated 13 novel structures of C30 carotenoids and one C35 carotenoid, including acyclic, monocyclic, and bicyclic structures, through directed evolution and combinatorial biosynthesis, in Escherichia coli. Measurement of radical scavenging activity of various C30 carotenoid structures revealed that acyclic C30 carotenoids showed higher radical scavenging activity than did DL-α-tocopherol. We could assume high potential biological activity of the novel structures of C30 carotenoids as well, based on the neuronal differentiation activity observed for the monocyclic C30 carotenoid 4,4'-diapotorulene on rat bone marrow mesenchymal stem cells. Our results demonstrate that a series of structurally novel carotenoids possessing biologically beneficial properties can be synthesized in E. coli.
NASA Astrophysics Data System (ADS)
Lu, Xujie; Hu, Qingyang; Yang, Wenge; Bai, Ligang; Sheng, Howard; Wang, Lin; Huang, Fuqiang; Wen, Jianguo; Miller, Dean; Zhao, Yusheng
2014-03-01
Pressure-induced amorphization (PIA) in single-crystal Ta2O5 nanowires is observed at 19 GPa and the obtained amorphous Ta2O5 nanowires show significant improvement in electrical conductivity. The phase transition process is unveiled by monitoring structural evolution with in-situ synchrotron XRD, PDF, Raman spectroscopy and TEM. The first principles calculations reveal the phonon modes softening during compression at particular bonds, and the analysis on the electron localization function also shows bond strength weakening at the same positions. Based on the experimental and theoretical results, a kinetic PIA mechanism is proposed and demonstrated systematically that amorphization is initiated by the disruption of connectivity between polyhedra at the particular weak-bonding positions along the a-axis in the unit cell. The one-dimensional morphology is well preserved for the pressure-induced amorphous Ta2O5 and the electrical conductivity is improved by an order of magnitude compared to traditional amorphous forms.
Emerging engineering principles for yield improvement in microbial cell design.
Comba, Santiago; Arabolaza, Ana; Gramajo, Hugo
2012-01-01
Metabolic Engineering has undertaken a rapid transformation in the last ten years making real progress towards the production of a wide range of molecules and fine chemicals using a designed cellular host. However, the maximization of product yields through pathway optimization is a constant and central challenge of this field. Traditional methods used to improve the production of target compounds from engineered biosynthetic pathways in non-native hosts include: codon usage optimization, elimination of the accumulation of toxic intermediates or byproducts, enhanced production of rate-limiting enzymes, selection of appropriate promoter and ribosome binding sites, application of directed evolution of enzymes, and chassis re-circuit. Overall, these approaches tend to be specific for each engineering project rather than a systematic practice based on a more generalizable strategy. In this mini-review, we highlight some novel and extensive approaches and tools intended to address the improvement of a target product formation, founded in sophisticated principles such as dynamic control, pathway genes modularization, and flux modeling.
Emerging engineering principles for yield improvement in microbial cell design
Comba, Santiago; Arabolaza, Ana; Gramajo, Hugo
2012-01-01
Metabolic Engineering has undertaken a rapid transformation in the last ten years making real progress towards the production of a wide range of molecules and fine chemicals using a designed cellular host. However, the maximization of product yields through pathway optimization is a constant and central challenge of this field. Traditional methods used to improve the production of target compounds from engineered biosynthetic pathways in non-native hosts include: codon usage optimization, elimination of the accumulation of toxic intermediates or byproducts, enhanced production of rate-limiting enzymes, selection of appropriate promoter and ribosome binding sites, application of directed evolution of enzymes, and chassis re-circuit. Overall, these approaches tend to be specific for each engineering project rather than a systematic practice based on a more generalizable strategy. In this mini-review, we highlight some novel and extensive approaches and tools intended to address the improvement of a target product formation, founded in sophisticated principles such as dynamic control, pathway genes modularization, and flux modeling. PMID:24688676
Trochet, Mickaël; Béland, Laurent Karim; Joly, Jean -François; ...
2015-06-16
We study point-defect diffusion in crystalline silicon using the kinetic activation-relaxation technique (k-ART), an off-lattice kinetic Monte Carlo method with on-the-fly catalog building capabilities based on the activation-relaxation technique (ART nouveau), coupled to the standard Stillinger-Weber potential. We focus more particularly on the evolution of crystalline cells with one to four vacancies and one to four interstitials in order to provide a detailed picture of both the atomistic diffusion mechanisms and overall kinetics. We show formation energies, activation barriers for the ground state of all eight systems, and migration barriers for those systems that diffuse. Additionally, we characterize diffusion pathsmore » and special configurations such as dumbbell complex, di-interstitial (IV-pair+2I) superdiffuser, tetrahedral vacancy complex, and more. In conclusion, this study points to an unsuspected dynamical richness even for this apparently simple system that can only be uncovered by exhaustive and systematic approaches such as the kinetic activation-relaxation technique.« less
Hemispheric asymmetry in coronal hole evolution: Cause of the bashful ballerina?
NASA Astrophysics Data System (ADS)
Mursula, K.; Tlatov, A.; Virtanen, I.
2012-12-01
The magnetic hemisphere prevalent in the solar northern hemisphere has been shown to cover a larger area than in the south for about three years in the declining phase of several solar cycles. Correspondingly, the average field intensity is weaker in the northern hemisphere and the heliospheric current sheet (HCS) is shifted southward at these times. This phenomenon, now called the bashful ballerina, has been verified using several databases and methods, including the in situ observations of the heliospheric magnetic field (HMF) at 1 AU by the OMNI data base, at about 2 AU by the Ulysses probe, and at different radial distances by the Voyager 1 and 2 and Pioneer 10 and 11 probes. The Ulysses observations show that the mean southward shift of the HCS was about 2 degrees in the declining phase of both cycle 22 and cycle 23, although the polar strengths were very different between the two cycles. The HMF observations by the Voyager and Pioneer probes show a very consistent structure of HMF sectors and HCS location in the entire heliosphere, and even beyond the termination shock. Moreover, they suggest a systematic difference in the development of northern and southern polar coronal holes. While the northern coronal holes developed very systematically during all the four solar minima since mid-1970s, the evolution of southern coronal holes was less systematic and delayed with respect to the northern hemisphere. This delay in the evolution of southern coronal holes leads to a larger extent of northern coronal holes and a southward shift of the heliospheric current sheet (the bashful ballerina phenomenon) for a few years in the declining phase of the solar cycle. Here we study direct observations of solar coronal holes and verify this difference in the evolution of coronal holes between the two solar hemispheres, which explains the bashful ballerina phenomenon.
Teaching Cell Division: Basics and Recommendations.
ERIC Educational Resources Information Center
Smith, Mike U.; Kindfield, Ann C. H.
1999-01-01
Presents a concise overview of cell division that includes only the essential concepts necessary for understanding genetics and evolution. Makes recommendations based on published research and teaching experiences that can be used to judge the merits of potential activities and materials for teaching cell division. Makes suggestions regarding the…
Evolution of the Calcium-Based Intracellular Signaling System
Marchadier, Elodie; Oates, Matt E.; Fang, Hai; Donoghue, Philip C.J.; Hetherington, Alistair M.; Gough, Julian
2016-01-01
To progress our understanding of molecular evolution from a collection of well-studied genes toward the level of the cell, we must consider whole systems. Here, we reveal the evolution of an important intracellular signaling system. The calcium-signaling toolkit is made up of different multidomain proteins that have undergone duplication, recombination, sequence divergence, and selection. The picture of evolution, considering the repertoire of proteins in the toolkit of both extant organisms and ancestors, is radically different from that of other systems. In eukaryotes, the repertoire increased in both abundance and diversity at a far greater rate than general genomic expansion. We describe how calcium-based intracellular signaling evolution differs not only in rate but in nature, and how this correlates with the disparity of plants and animals. PMID:27358427
Systematic review of renal carcinoma prognostic factors.
Lorente, D; Trilla, E; Meseguer, A; Planas, J; Placer, J; Celma, A; Salvador, C; Regis, L; Morote, J
2017-05-01
The natural history of renal cell carcinoma is heterogeneous. Some scenarios can be found in terms of clinical presentation, clinical evolution or type of recurrence (local/metastatic). The aim of this publication is to analyze the most important prognostic factors published in the literature. A literature review ob published papers was performed using the Pubmed, from first Motzer's classification published in 1999 to 2015, according to PRISMA declaration. Search was done using the following keywords: kidney neoplasm, kidney cancer, renal cell carcinoma, prognostic factors, mortality, survival and disease progression. Papers were classified according to level of evidence, the number of patients included and the type of study performed. The evolution in the knowledge of molecular pathways related to renal oncogenesis and the new targeted therapies has left to remain obsolete the old prognostic models. It's necessary to perform a continuous review to actualize nomograms and to adapt them to the new scenarios. Is necessary to perform a proper external validation of existing prognostic factors using prospective and multicentric studies to add them into the daily urologist clinical practice. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.
NASA Astrophysics Data System (ADS)
Deng, J.; Sanford, R. A.; Dong, Y.; Shechtman, L. A.; Zhou, L.; Alcalde, R.; Werth, C. J.; Fouke, B. W.
2016-12-01
Microorganisms in nature have evolved in response to a variety of environmental stresses, including gradients of temperature, pH, substrate availability and aqueous chemistry. While environmental stresses are considered to be the driving forces of adaptive evolution, the impact and extent of any specific stress needed to drive such changes has not been well characterized. In this study, the antibiotic Ciprofloxacin was used as a stressor and systematically applied to E. coli st. 307 cells via a spatial gradient in a microfluidic pore network and a temporal gradient in batch cultures. The microfluidic device facilitated in vitro real-time tracking of bacterial abundances and dynamic spatial distributions in response to the gradients of both the antibiotic and nutrients. Cells collected from the microfluidic device showed growth on plates containing up to 10-times the original minimum inhibition concentration (MIC). In batch systems, Ciprofloxacin was used to evaluate adaptive responses via temporal gradients, in which the stressor concentration was incrementally increased over time with each transfer of the culture after 24 hours of growth. Responses of E. coli 307 to these stress patterns were measured by quantifying changes in the MIC for Ciprofloxacin. Over a period of 18 days of step-wise concentration increments, bacterial cells were observed to acquire tolerance gradually and eventually adapt to a 28-fold increase in the original MIC. Samples at different stages within the temporal Ciprofloxacin gradient treatment show different extents of resistance. All samples exhibited resistance exceeding the highest exposure stress concentration. In combination with the spatial and temporal gradient systems, this work provides the first comprehensive measure of the dynamic resistance of E. coli in response to Ciprofloxacin concentration gradients. These will provide invaluable insights to understand the effects of antibiotic stresses on bacterial adaptive evolution in medical settings and shed light on understanding the mechanics of microbial evolution.
NASA Astrophysics Data System (ADS)
Arunchander, A.; Peera, S. Gouse; Sahu, A. K.
2017-06-01
Nanostructured transition metal chalcogenides (TMCs) have significant interest towards electrochemical devices such as fuel cells, metal-ion batteries, due to their unique physical and electrochemical properties. Herein, we report a facile hydrothermal synthesis of flower-like nanostructured molybdenum sulphide and its incorporation on to graphene as a potential oxygen reduction reaction catalyst in alkaline medium. The phase purity and morphological evolution of MoS2 is systematically studied through X-ray diffraction and scanning electron microscopic techniques. The electronic states of metal and non-metallic species are deeply studied by X-ray photoelectron spectroscopy. The effect of annealing temperatures and TMC concentrations are also investigated by electrochemical techniques such as cyclic and linear sweep voltammograms. The optimised electrocatalyst (MoS2/G-500) delivers significant ORR activity with onset and half-wave potentials of 0.91 and 0.80 V (vs. RHE), respectively. Superior durability compared to state-of-art Pt/C catalyst is ascertained by repeating potential cycles for about 5000 times and also by chronoamperometric technique. Finally, the hybrid catalyst is evaluated in AEMFC as cathode catalyst which delivers peak power density of about 29 mW cm-2 under ambient temperature and pressure. The present findings emphasis that MoS2/G catalyst is promising as cost-effective and alternative to noble metal-based catalysts for fuel cell applications.
Time evolution of gamma rays from supernova remnants
NASA Astrophysics Data System (ADS)
Gaggero, Daniele; Zandanel, Fabio; Cristofari, Pierre; Gabici, Stefano
2018-04-01
We present a systematic phenomenological study focused on the time evolution of the non-thermal radiation - from radio waves to gamma rays - emitted by typical supernova remnants via hadronic and leptonic mechanisms, for two classes of progenitors: thermonuclear and core-collapse. To this aim, we develop a numerical tool designed to model the evolution of the cosmic ray spectrum inside a supernova remnant, and compute the associated multi-wavelength emission. We demonstrate the potential of this tool in the context of future population studies based on large collection of high-energy gamma-ray data. We discuss and explore the relevant parameter space involved in the problem, and focus in particular on their impact on the maximum energy of accelerated particles, in order to study the effectiveness and duration of the PeVatron phase. We outline the crucial role of the ambient medium through which the shock propagates during the remnant evolution. In particular, we point out the role of dense clumps in creating a significant hardening in the hadronic gamma-ray spectrum.
A miniaturized, optically accessible bioreactor for systematic 3D tissue engineering research.
Laganà, Matteo; Raimondi, Manuela T
2012-02-01
Perfusion bioreactors are widely used in tissue engineering and pharmaceutical research to provide reliable models of tissue growth under controlled conditions. Destructive assays are not able to follow the evolution of the growing tissue on the same construct, so it is necessary to adopt non-destructive analysis. We have developed a miniaturized, optically accessible bioreactor for interstitial perfusion of 3D cell-seeded scaffolds. The scaffold adopted was optically transparent, with highly defined architecture. Computational fluid dynamics (CFD) analysis was useful to predict the flow behavior in the bioreactor scaffold chamber (that was laminar flow, Re = 0.179, with mean velocity equal to 100 microns/s). Moreover, experimental characterization of the bioreactor performance gave that the maximum allowable pressure was 0.06 MPa and allowable flow rate up to 25 ml/min. A method, to estimate quantitatively and non destructively the cell proliferation (from 15 to 43 thousand cells) and tissue growth (from 2% to 43%) during culture time, was introduced and validated. An end point viability test was performed to check the experimental set-up overall suitability for cell culture with successful results. Morphological analysis was performed at the end time point to show the complex tridimensional pattern of the biological tissue growth. Our system, characterized by controlled conditions in a wide range of allowable flow rate and pressure, permits to systematically study the influence of several parameters on engineered tissue growth, using viable staining and a standard fluorescence microscope.
Clinical applications of cell-based approaches in alveolar bone augmentation: a systematic review.
Shanbhag, Siddharth; Shanbhag, Vivek
2015-01-01
Cell-based approaches, utilizing adult mesenchymal stem cells (MSCs), are reported to overcome the limitations of conventional bone augmentation procedures. The study aims to systematically review the available evidence on the characteristics and clinical effectiveness of cell-based ridge augmentation, socket preservation, and sinus-floor augmentation, compared to current evidence-based methods in human adult patients. MEDLINE, EMBASE, and CENTRAL databases were searched for related literature. Both observational and experimental studies reporting outcomes of "tissue engineered" or "cell-based" augmentation in ≥5 adult patients alone, or in comparison with non-cell-based (conventional) augmentation methods, were eligible for inclusion. Primary outcome was histomorphometric analysis of new bone formation. Effectiveness of cell-based augmentation was evaluated based on outcomes of controlled studies. Twenty-seven eligible studies were identified. Of these, 15 included a control group (8 randomized controlled trials [RCTs]), and were judged to be at a moderate-to-high risk of bias. Most studies reported the combined use of cultured autologous MSCs with an osteoconductive bone substitute (BS) scaffold. Iliac bone marrow and mandibular periosteum were frequently reported sources of MSCs. In vitro culture of MSCs took between 12 days and 1.5 months. A range of autogenous, allogeneic, xenogeneic, and alloplastic scaffolds was identified. Bovine bone mineral scaffold was frequently reported with favorable outcomes, while polylactic-polyglycolic acid copolymer (PLGA) scaffold resulted in graft failure in three studies. The combination of MSCs and BS resulted in outcomes similar to autogenous bone (AB) and BS. Three RCTs and one controlled trial reported significantly greater bone formation in cell-based than conventionally grafted sites after 3 to 8 months. Based on limited controlled evidence at a moderate-to-high risk of bias, cell-based approaches are comparable, if not superior, to current evidence-based bone grafting methods, with a significant advantage of avoiding AB harvesting. Future clinical trials should additionally evaluate patient-based outcomes and the time-/cost-effectiveness of these approaches. © 2013 Wiley Periodicals, Inc.
Nowak, Martin A.; Krakauer, David C.
1999-01-01
The emergence of language was a defining moment in the evolution of modern humans. It was an innovation that changed radically the character of human society. Here, we provide an approach to language evolution based on evolutionary game theory. We explore the ways in which protolanguages can evolve in a nonlinguistic society and how specific signals can become associated with specific objects. We assume that early in the evolution of language, errors in signaling and perception would be common. We model the probability of misunderstanding a signal and show that this limits the number of objects that can be described by a protolanguage. This “error limit” is not overcome by employing more sounds but by combining a small set of more easily distinguishable sounds into words. The process of “word formation” enables a language to encode an essentially unlimited number of objects. Next, we analyze how words can be combined into sentences and specify the conditions for the evolution of very simple grammatical rules. We argue that grammar originated as a simplified rule system that evolved by natural selection to reduce mistakes in communication. Our theory provides a systematic approach for thinking about the origin and evolution of human language. PMID:10393942
Jühling, Frank; Pütz, Joern; Bernt, Matthias; Donath, Alexander; Middendorf, Martin; Florentz, Catherine; Stadler, Peter F.
2012-01-01
Transfer RNAs (tRNAs) are present in all types of cells as well as in organelles. tRNAs of animal mitochondria show a low level of primary sequence conservation and exhibit ‘bizarre’ secondary structures, lacking complete domains of the common cloverleaf. Such sequences are hard to detect and hence frequently missed in computational analyses and mitochondrial genome annotation. Here, we introduce an automatic annotation procedure for mitochondrial tRNA genes in Metazoa based on sequence and structural information in manually curated covariance models. The method, applied to re-annotate 1876 available metazoan mitochondrial RefSeq genomes, allows to distinguish between remaining functional genes and degrading ‘pseudogenes’, even at early stages of divergence. The subsequent analysis of a comprehensive set of mitochondrial tRNA genes gives new insights into the evolution of structures of mitochondrial tRNA sequences as well as into the mechanisms of genome rearrangements. We find frequent losses of tRNA genes concentrated in basal Metazoa, frequent independent losses of individual parts of tRNA genes, particularly in Arthropoda, and wide-spread conserved overlaps of tRNAs in opposite reading direction. Direct evidence for several recent Tandem Duplication-Random Loss events is gained, demonstrating that this mechanism has an impact on the appearance of new mitochondrial gene orders. PMID:22139921
Raman spectra of Hg-based superconductors: Effect of oxygen defects
NASA Astrophysics Data System (ADS)
Zhou, Xingjiang; Cardona, M.; Chu, C. W.; Lin, Q. M.; Loureiro, S. M.; Marezio, M.
1996-09-01
Polarized micro-Raman scattering measurements have been performed on the five members of the HgBa2Can-1CunO2n+2+δ (n=1, 2, 3, 4, and 5) high-Tc superconductor family. A systematic evolution of the spectrum, which mainly involves oxygen-related phonons around 590, 570, 540, and 470 cm-1, with an increasing number of CuO2 layers, has been observed. Local laser annealing measurements clearly demonstrate that all these phonons are closely related to interstitial oxygen in the HgOδ planes. The origin of the spectrum evolution with the number of CuO2 layers lies in the variation of interstitial oxygen content.
NASA Technical Reports Server (NTRS)
Stein, M.
1988-01-01
The evolution of the upper-mantle and the lower-crust (the conteinental lithosphere), is the area of Israel and Sinai was studied, using the chemical composition and the Nd-Sr isotopic systematics from mantle and crustal nodules, their host basalts, and granites. The magmatism and the metasomatism making the lithosphere are related to uprise of mantle diapirs in the uppermost mantle of the area. These diapirs heated the base of the lithosphere, eroded, and replaced it with new hot material. It caused a domal uplift of the lithosphere (and the crust). The doming resulted in tensional stresses that in turn might develop transport channels for the basalt.
B4C as a stable non-carbon-based oxygen electrode material for lithium-oxygen batteries
DOE Office of Scientific and Technical Information (OSTI.GOV)
Song, Shidong; Xu, Wu; Cao, Ruiguo
Lithium-oxygen (Li-O 2) batteries have extremely high theoretical specific capacities and energy densities when compared with Li-ion batteries. However, the instability of both electrolyte and carbon-based oxygen electrode related to the nucleophilic attack of reduced oxygen species during oxygen reduction reaction and the electrochemical oxidation during oxygen evolution reaction are recognized as the major challenges in this field. Here we report the application of boron carbide (B 4C) as the non-carbon based oxygen electrode material for aprotic Li-O 2 batteries. B 4C has high resistance to chemical attack, good conductivity, excellent catalytic activity and low density that are suitable formore » battery applications. The electrochemical activity and chemical stability of B4C are systematically investigated in aprotic electrolyte. Li-O 2 cells using B4C based air electrodes exhibit better cycling stability than those used TiC based air electrode in 1 M LiTf-Tetraglyme electrolyte. The degradation of B 4C based electrode is mainly due to be the loss of active sites on B 4C electrode during cycles as identified by the structure and composition characterizations. These results clearly demonstrate that B 4C is a very promising alternative oxygen electrode material for aprotic Li-O 2 batteries. It can also be used as a standard electrode to investigate the stability of electrolytes.« less
Chisholm, Rebecca H; Lorenzi, Tommaso; Clairambault, Jean
2016-11-01
Drug-induced drug resistance in cancer has been attributed to diverse biological mechanisms at the individual cell or cell population scale, relying on stochastically or epigenetically varying expression of phenotypes at the single cell level, and on the adaptability of tumours at the cell population level. We focus on intra-tumour heterogeneity, namely between-cell variability within cancer cell populations, to account for drug resistance. To shed light on such heterogeneity, we review evolutionary mechanisms that encompass the great evolution that has designed multicellular organisms, as well as smaller windows of evolution on the time scale of human disease. We also present mathematical models used to predict drug resistance in cancer and optimal control methods that can circumvent it in combined therapeutic strategies. Plasticity in cancer cells, i.e., partial reversal to a stem-like status in individual cells and resulting adaptability of cancer cell populations, may be viewed as backward evolution making cancer cell populations resistant to drug insult. This reversible plasticity is captured by mathematical models that incorporate between-cell heterogeneity through continuous phenotypic variables. Such models have the benefit of being compatible with optimal control methods for the design of optimised therapeutic protocols involving combinations of cytotoxic and cytostatic treatments with epigenetic drugs and immunotherapies. Gathering knowledge from cancer and evolutionary biology with physiologically based mathematical models of cell population dynamics should provide oncologists with a rationale to design optimised therapeutic strategies to circumvent drug resistance, that still remains a major pitfall of cancer therapeutics. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang. Copyright © 2016 Elsevier B.V. All rights reserved.
Gourronc, Francoise A.; Rockey, William M.; Thiel, William H.; Giangrande, Paloma H.; Klingelhutz, Aloysius J.
2013-01-01
Human papillomavirus type 16 (HPV-16) associated oropharyngeal cancers are on a significant increase and better therapeutic strategies are needed. The HPV-16 oncogenes E6 and E7 are expressed in HPV-associated cancers and are able to transform human tonsillar epithelial cells (HTECs). We used cell-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) to select for RNA aptamers that entered into HPV-16 E6/E7-HTECs. After 12 rounds of cell-SELEX, a pool of aptamers was obtained that had significantly greater internalization capacity (~5-fold) into E6/E7-HTECs as compared to primary HTECs or fibroblasts. Analysis of individual aptamers from the pool indicated variable internalization into E6/E7-HTECs (1 to 8-fold as compared to a negative control). Most of the individual aptamers internalized into E6/E7 and primary HTECs with similar efficiency, while one aptamer exhibited ~3-fold better internalization into E6/E7-HTECs. Aptamers that internalize into cells may be useful for delivering therapeutic agents to HPV-16 associated malignancies. PMID:24074596
Reppetto, Maria Angela; de Souza, Mariana Fernandes
2005-01-01
This descriptive study was carried out in a teaching hospital at São Paulo city and had as objective to identify the phases performance and registration of nursing care systematization and the most frequent nursing diagnoses. Data were collected retrospectively from 135 patients records of three units: Cardiology, Adult Infectious Diseases and Neurosurgery, from January to July, 2002. The phases: history, nursing diagnoses, prescription, evolution and assessment were performed and registered in the three units, however, it was verified systematization gaps performance related to nursing diagnoses registered without the realization of nursing history and nursing prescriptions without evolution. The most frequent nursing diagnosis in the three units was risk for infection.
Biomedical Biopolymers, their Origin and Evolution in Biomedical Sciences: A Systematic Review
Yadav, Harsh; Shah, Veena Gowri; Shah, Gaurav; Dhaka, Gaurav
2015-01-01
Biopolymers provide a plethora of applications in the pharmaceutical and medical applications. A material that can be used for biomedical applications like wound healing, drug delivery and tissue engineering should possess certain properties like biocompatibility, biodegradation to non-toxic products, low antigenicity, high bio-activity, processability to complicated shapes with appropriate porosity, ability to support cell growth and proliferation and appropriate mechanical properties, as well as maintaining mechanical strength. This paper reviews biodegradable biopolymers focusing on their potential in biomedical applications. Biopolymers most commonly used and most abundantly available have been described with focus on the properties relevant to biomedical importance. PMID:26501034
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lorenzi, Tommaso; Chisholm, Rebecca H.; Lorz, Alexander
We formulate an individual-based model and a population model of phenotypic evolution, under cytotoxic drugs, in a cancer cell population structured by the expression levels of survival-potential and proliferation-potential. We apply these models to a recently studied experimental system. Our results suggest that mechanisms based on fundamental laws of biology can reversibly push an actively-proliferating, and drug-sensitive, cell population to transition into a weakly-proliferative and drug-tolerant state, which will eventually facilitate the emergence of more potent, proliferating and drug-tolerant cells.
Methods for constraining fine structure constant evolution with OH microwave transitions.
Darling, Jeremy
2003-07-04
We investigate the constraints that OH microwave transitions in megamasers and molecular absorbers at cosmological distances may place on the evolution of the fine structure constant alpha=e(2)/ variant Planck's over 2pi c. The centimeter OH transitions are a combination of hyperfine splitting and lambda doubling that can constrain the cosmic evolution of alpha from a single species, avoiding systematic errors in alpha measurements from multiple species which may have relative velocity offsets. The most promising method compares the 18 and 6 cm OH lines, includes a calibration of systematic errors, and offers multiple determinations of alpha in a single object. Comparisons of OH lines to the HI 21 cm line and CO rotational transitions also show promise.
NASA Astrophysics Data System (ADS)
Kim, Kyoohyun; Yoon, HyeOk; Diez-Silva, Monica; Dao, Ming; Dasari, Ramachandra R.; Park, YongKeun
2014-01-01
We present high-resolution optical tomographic images of human red blood cells (RBC) parasitized by malaria-inducing Plasmodium falciparum (Pf)-RBCs. Three-dimensional (3-D) refractive index (RI) tomograms are reconstructed by recourse to a diffraction algorithm from multiple two-dimensional holograms with various angles of illumination. These 3-D RI tomograms of Pf-RBCs show cellular and subcellular structures of host RBCs and invaded parasites in fine detail. Full asexual intraerythrocytic stages of parasite maturation (ring to trophozoite to schizont stages) are then systematically investigated using optical diffraction tomography algorithms. These analyses provide quantitative information on the structural and chemical characteristics of individual host Pf-RBCs, parasitophorous vacuole, and cytoplasm. The in situ structural evolution and chemical characteristics of subcellular hemozoin crystals are also elucidated.
Kim, Kyoohyun; Yoon, HyeOk; Diez-Silva, Monica; Dao, Ming; Dasari, Ramachandra R.
2013-01-01
Abstract. We present high-resolution optical tomographic images of human red blood cells (RBC) parasitized by malaria-inducing Plasmodium falciparum (Pf)-RBCs. Three-dimensional (3-D) refractive index (RI) tomograms are reconstructed by recourse to a diffraction algorithm from multiple two-dimensional holograms with various angles of illumination. These 3-D RI tomograms of Pf-RBCs show cellular and subcellular structures of host RBCs and invaded parasites in fine detail. Full asexual intraerythrocytic stages of parasite maturation (ring to trophozoite to schizont stages) are then systematically investigated using optical diffraction tomography algorithms. These analyses provide quantitative information on the structural and chemical characteristics of individual host Pf-RBCs, parasitophorous vacuole, and cytoplasm. The in situ structural evolution and chemical characteristics of subcellular hemozoin crystals are also elucidated. PMID:23797986
DOE Office of Scientific and Technical Information (OSTI.GOV)
Huang, Hongwei; Cao, Ranran; Yu, Shixin
Single-layer catalysis sparks huge interests and gains widespread attention owing to its high activity. Simultaneously, three-dimensional (3D) hierarchical structure can afford large surface area and abundant reactive sites, contributing to high efficiency. Herein, we report an absorbing single-unit-cell layer established Bi2WO6 3D hierarchical architecture fabricated by a sodium dodecyl benzene sulfonate (SDBS)-assisted assembled strategy. The DBS- long chains can adsorb on the (Bi2O2)2+ layers and hence impede stacking of the layers, resulting in the single-unit-cell layer. We also uncovered that SDS with a shorter chain is less effective than SDBS. Due to the sufficient exposure of surface O atoms, single-unit-cellmore » layer 3D Bi2WO6 shows strong selectivity for adsorption on multiform organic dyes with different charges. Remarkably, the single-unit-cell layer 3D Bi2WO6 casts profoundly enhanced photodegradation activity and especially a superior photocatalytic H2 evolution rate, which is 14-fold increase in contrast to the bulk Bi2WO6. Systematic photoelectrochemical characterizations disclose that the substantially elevated carrier density and charge separation efficiency take responsibility for the strengthened photocatalytic performance. Additionally, the possibility of single-unit-cell layer 3D Bi2WO6 as dye-sensitized solar cells (DSSC) has also been attempted and it was manifested to be a promising dye-sensitized photoanode for oxygen evolution reaction (ORR). Our work not only furnish an insight into designing single-layer assembled 3D hierarchical architecture, but also offer a multi-functional material for environmental and energy applications.« less
Between-Region Genetic Divergence Reflects the Mode and Tempo of Tumor Evolution
Sun, Ruping; Hu, Zheng; Sottoriva, Andrea; Graham, Trevor A.; Harpak, Arbel; Ma, Zhicheng; Fischer, Jared M.; Shibata, Darryl; Curtis, Christina
2017-01-01
Given the implications of tumor dynamics for precision medicine, there is a need to systematically characterize the mode of evolution across diverse solid tumor types. In particular, methods to infer the role of natural selection within established human tumors are lacking. By simulating spatial tumor growth under different evolutionary modes and examining patterns of between-region subclonal genetic divergence from multi-region sequencing (MRS) data, we demonstrate that it is feasible to distinguish tumors driven by strong positive subclonal selection from those evolving neutrally or under weak selection, as the latter fail to dramatically alter subclonal composition. We developed a classifier based on measures of between-region subclonal genetic divergence and projected patient data into model space, revealing different modes of evolution both within and between solid tumor types. Our findings have broad implications for how human tumors progress, accumulate intra-tumor heterogeneity, and ultimately how they may be more effectively treated. PMID:28581503
Fast multi-dimensional NMR by minimal sampling
NASA Astrophysics Data System (ADS)
Kupče, Ēriks; Freeman, Ray
2008-03-01
A new scheme is proposed for very fast acquisition of three-dimensional NMR spectra based on minimal sampling, instead of the customary step-wise exploration of all of evolution space. The method relies on prior experiments to determine accurate values for the evolving frequencies and intensities from the two-dimensional 'first planes' recorded by setting t1 = 0 or t2 = 0. With this prior knowledge, the entire three-dimensional spectrum can be reconstructed by an additional measurement of the response at a single location (t1∗,t2∗) where t1∗ and t2∗ are fixed values of the evolution times. A key feature is the ability to resolve problems of overlap in the acquisition dimension. Applied to a small protein, agitoxin, the three-dimensional HNCO spectrum is obtained 35 times faster than systematic Cartesian sampling of the evolution domain. The extension to multi-dimensional spectroscopy is outlined.
Anatomy of scientific evolution.
Yun, Jinhyuk; Kim, Pan-Jun; Jeong, Hawoong
2015-01-01
The quest for historically impactful science and technology provides invaluable insight into the innovation dynamics of human society, yet many studies are limited to qualitative and small-scale approaches. Here, we investigate scientific evolution through systematic analysis of a massive corpus of digitized English texts between 1800 and 2008. Our analysis reveals great predictability for long-prevailing scientific concepts based on the levels of their prior usage. Interestingly, once a threshold of early adoption rates is passed even slightly, scientific concepts can exhibit sudden leaps in their eventual lifetimes. We developed a mechanistic model to account for such results, indicating that slowly-but-commonly adopted science and technology surprisingly tend to have higher innate strength than fast-and-commonly adopted ones. The model prediction for disciplines other than science was also well verified. Our approach sheds light on unbiased and quantitative analysis of scientific evolution in society, and may provide a useful basis for policy-making.
Anatomy of Scientific Evolution
Yun, Jinhyuk; Kim, Pan-Jun; Jeong, Hawoong
2015-01-01
The quest for historically impactful science and technology provides invaluable insight into the innovation dynamics of human society, yet many studies are limited to qualitative and small-scale approaches. Here, we investigate scientific evolution through systematic analysis of a massive corpus of digitized English texts between 1800 and 2008. Our analysis reveals great predictability for long-prevailing scientific concepts based on the levels of their prior usage. Interestingly, once a threshold of early adoption rates is passed even slightly, scientific concepts can exhibit sudden leaps in their eventual lifetimes. We developed a mechanistic model to account for such results, indicating that slowly-but-commonly adopted science and technology surprisingly tend to have higher innate strength than fast-and-commonly adopted ones. The model prediction for disciplines other than science was also well verified. Our approach sheds light on unbiased and quantitative analysis of scientific evolution in society, and may provide a useful basis for policy-making. PMID:25671617
Pettitt, David; Arshad, Zeeshaan; Davies, Benjamin; Smith, James; French, Anna; Cole, Doug; Bure, Kim; Dopson, Sue; DiGiusto, David; Karp, Jeff; Reeve, Brock; Barker, Richard; Holländer, Georg; Brindley, David
2017-06-26
Cellular-based therapies represent a platform technology within the rapidly expanding field of regenerative medicine and are distinct from conventional therapeutics-offering a unique approach to managing what were once considered untreatable diseases. Despite a significant increase in basic science activity within the cell therapy arena, alongside a growing portfolio of cell therapy trials and promising investment, the translation of cellular-based therapeutics from "bench to bedside" remains challenging, and the number of industry products available for widespread clinical use remains comparatively low. This systematic review identifies unique intrinsic and extrinsic barriers in the cell-based therapy domain. Eight electronic databases will be searched, specifically Medline, EMBASE (OvidSP), BIOSIS & Web of Science, Cochrane Library & HEED, EconLit (ProQuest), WHOLIS WHO Library Database, PAIS International (ProQuest), and Scopus. Addition to this gray literature was searched by manually reviewing relevant work. All identified articles will be subjected for review by two authors who will decide whether or not each article passes our inclusion/exclusion criteria. Eligible papers will subsequently be reviewed, and key data extracted into a pre-designed data extraction scorecard. An assessment of the perceived impact of broad commercial barriers to the adoption of cell-based therapies will be conducted. These broad categories will include manufacturing, regulation and intellectual property, reimbursement, clinical trials, clinical adoption, ethics, and business models. This will inform further discussion in the review. There is no PROSPERO registration number. Through a systematic search and appraisal of available literature, this review will identify key challenges in the commercialization pathway of cellular-based therapeutics and highlights significant barriers impeding successful clinical adoption. This will aid in creating an adaptable, acceptable, and harmonized approach supported by apposite regulatory frameworks and pertinent expertise throughout the respective stages of the adoption cycle to facilitate the adoption of new products and technologies in the industry.
NASA Astrophysics Data System (ADS)
Tomlins, Peter H.; Rahman, Mohammed Wahidur; Donnan, Robert S.
2016-04-01
This study aimed to determine the feasibility of using optical coherence elastography to measure internal displacements during the curing phase of a light-activated, resin-based composite material. Displacement vectors were spatially mapped over time within a commercial dental composite. Measurements revealed that the orientation of cure-induced displacement vectors varied spatially in a complex manner; however, each vector showed a systematic evolution with time. Precision of individual displacements was estimated to be ˜1 to 2 μm, enabling submicrometer time-varying displacements to be detected.
Nomura, Yusuke; Tanaka, Yoichiro; Fukunaga, Jun-ichi; Fujiwara, Kazuya; Chiba, Manabu; Iibuchi, Hiroaki; Tanaka, Taku; Nakamura, Yoshikazu; Kawai, Gota; Kozu, Tomoko; Sakamoto, Taiichi
2013-12-01
AML1/RUNX1 is an essential transcription factor involved in the differentiation of hematopoietic cells. AML1 binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. In a previous study, we obtained RNA aptamers against the AML1 Runt domain by systematic evolution of ligands by exponential enrichment and revealed that RNA aptamers exhibit higher affinity for the Runt domain than that for RDE and possess the 5'-GCGMGNN-3' and 5'-N'N'CCAC-3' conserved motif (M: A or C; N and N' form Watson-Crick base pairs) that is important for Runt domain binding. In this study, to understand the structural basis of recognition of the Runt domain by the aptamer motif, the solution structure of a 22-mer RNA was determined using nuclear magnetic resonance. The motif contains the AH(+)-C mismatch and base triple and adopts an unusual backbone structure. Structural analysis of the aptamer motif indicated that the aptamer binds to the Runt domain by mimicking the RDE sequence and structure. Our data should enhance the understanding of the structural basis of DNA mimicry by RNA molecules.
The evolution of cell types in animals: emerging principles from molecular studies.
Arendt, Detlev
2008-11-01
Cell types are fundamental units of multicellular life but their evolution is obscure. How did the first cell types emerge and become distinct in animal evolution? What were the sets of cell types that existed at important evolutionary nodes that represent eumetazoan or bilaterian ancestors? How did these ancient cell types diversify further during the evolution of organ systems in the descending evolutionary lines? The recent advent of cell type molecular fingerprinting has yielded initial insights into the evolutionary interrelationships of cell types between remote animal phyla and has allowed us to define some first principles of cell type diversification in animal evolution.
Limsakul, Praopim; Peng, Qin; Wu, Yiqian; Allen, Molly E; Liang, Jing; Remacle, Albert G; Lopez, Tyler; Ge, Xin; Kay, Brian K; Zhao, Huimin; Strongin, Alex Y; Yang, Xiang-Lei; Lu, Shaoying; Wang, Yingxiao
2018-04-19
Monitoring enzymatic activities at the cell surface is challenging due to the poor efficiency of transport and membrane integration of fluorescence resonance energy transfer (FRET)-based biosensors. Therefore, we developed a hybrid biosensor with separate donor and acceptor that assemble in situ. The directed evolution and sequence-function analysis technologies were integrated to engineer a monobody variant (PEbody) that binds to R-phycoerythrin (R-PE) dye. PEbody was used for visualizing the dynamic formation/separation of intercellular junctions. We further fused PEbody with the enhanced CFP and an enzyme-specific peptide at the extracellular surface to create a hybrid FRET biosensor upon R-PE capture for monitoring membrane-type-1 matrix metalloproteinase (MT1-MMP) activities. This biosensor revealed asymmetric distribution of MT1-MMP activities, which were high and low at loose and stable cell-cell contacts, respectively. Therefore, directed evolution and rational design are promising tools to engineer molecular binders and hybrid FRET biosensors for monitoring molecular regulations at the surface of living cells. Copyright © 2018 Elsevier Ltd. All rights reserved.
Urban Evolution: the Role of Water
The structure, function, and services of urban ecosystems evolve over time scales from seconds to centuries as Earth's population grows, infrastructure ages, and sociopolitical values alter them. In order to systematically study changes over time, the concept of "urban evolution...
Evolution of food provision to athletes at the summer Olympic Games.
Pelly, Fiona E; O'Connor, Helen T; Denyer, Gareth S; Caterson, Ian D
2011-06-01
The history of food provision at the summer Olympic Games (OG) over the past century (1896-2008) provides insight into the evolution of sports nutrition research and the dietary strategies of athletes. Early research favoring protein as the main fuel for exercise was reflected in OG menus from 1932 to 1968. Despite conclusive research from the 1960s demonstrating the clear benefit of carbohydrate on exercise performance, a specific emphasis on carbohydrate-rich foods was not noted until the 1970s. Athlete food preferences and catering complexity evolved rapidly between 1970 and 2000, driven predominantly by a dramatic expansion of the OG and the emergence of systematic sports nutrition research. Nutritional advice by experts and sponsorship by food companies became increasingly important beginning with the 1984 Los Angeles OG. More recent developments include nutritional labeling of menu items and provision of a nutrition information desk (Barcelona 1992), demand for a "high-starch, low-fat menu" (Atlanta 1996), the addition of a dedicated menu website and the systematic gathering of information on athletes' apparent consumption (Sydney 2000), and appointment of the first international dietetic review committee (Beijing 2008). The history of catering at the OG tracks the evolution of sports nutrition practice from anecdotes and myth towards an established specialty in nutrition and dietetics grounded in evidence-based science. © 2011 International Life Sciences Institute.
Zhou, Nanjia; Dudnik, Alexander S; Li, Ting I N G; Manley, Eric F; Aldrich, Thomas J; Guo, Peijun; Liao, Hsueh-Chung; Chen, Zhihua; Chen, Lin X; Chang, Robert P H; Facchetti, Antonio; Olvera de la Cruz, Monica; Marks, Tobin J
2016-02-03
The influence of the number-average molecular weight (Mn) on the blend film morphology and photovoltaic performance of all-polymer solar cells (APSCs) fabricated with the donor polymer poly[5-(2-hexyldodecyl)-1,3-thieno[3,4-c]pyrrole-4,6-dione-alt-5,5-(2,5-bis(3-dodecylthiophen-2-yl)thiophene)] (PTPD3T) and acceptor polymer poly{[N,N'-bis(2-octyldodecyl)naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5'-(2,2'-bithiophene)} (P(NDI2OD-T2); N2200) is systematically investigated. The Mn effect analysis of both PTPD3T and N2200 is enabled by implementing a polymerization strategy which produces conjugated polymers with tunable Mns. Experimental and coarse-grain modeling results reveal that systematic Mn variation greatly influences both intrachain and interchain interactions and ultimately the degree of phase separation and morphology evolution. Specifically, increasing Mn for both polymers shrinks blend film domain sizes and enhances donor-acceptor polymer-polymer interfacial areas, affording increased short-circuit current densities (Jsc). However, the greater disorder and intermixed feature proliferation accompanying increasing Mn promotes charge carrier recombination, reducing cell fill factors (FF). The optimized photoactive layers exhibit well-balanced exciton dissociation and charge transport characteristics, ultimately providing solar cells with a 2-fold PCE enhancement versus devices with nonoptimal Mns. Overall, it is shown that proper and precise tuning of both donor and acceptor polymer Mns is critical for optimizing APSC performance. In contrast to reports where maximum power conversion efficiencies (PCEs) are achieved for the highest Mns, the present two-dimensional Mn optimization matrix strategy locates a PCE "sweet spot" at intermediate Mns of both donor and acceptor polymers. This study provides synthetic methodologies to predictably access conjugated polymers with desired Mn and highlights the importance of optimizing Mn for both polymer components to realize the full potential of APSC performance.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhou, Nanjia; Dudnik, Alexander S.; Li, Ting I. N. G.
2016-01-21
The influence of the number-average molecular weight (Mn) on the blend film morphology and photovoltaic performance of all-polymer solar cells (APSCs) fabricated with the donor polymer poly[5-(2-hexyldodecyl)-1,3-thieno[3,4-c]pyrrole-4,6-dione-alt-5,5-(2,5-bis(3-dodecylthiophen-2-yl)thiophene)] (PTPD3T) and acceptor polymer poly{[N,N'-bis(2-octyldodecyl)naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5'-(2,2'-bithiophene)} (P(NDI2OD-T2); N2200) is systematically investigated. The Mn effect analysis of both PTPD3T and N2200 is enabled by implementing a polymerization strategy which produces conjugated polymers with tunable Mns. Experimental and coarse-grain modeling results reveal that systematic Mn variation greatly influences both intrachain and interchain interactions and ultimately the degree of phase separation and morphology evolution. Specifically, increasing Mn for both polymers shrinks blend film domain sizes and enhancesmore » donor–acceptor polymer–polymer interfacial areas, affording increased short-circuit current densities (Jsc). However, the greater disorder and intermixed feature proliferation accompanying increasing Mn promotes charge carrier recombination, reducing cell fill factors (FF). The optimized photoactive layers exhibit well-balanced exciton dissociation and charge transport characteristics, ultimately providing solar cells with a 2-fold PCE enhancement versus devices with nonoptimal Mns. Overall, it is shown that proper and precise tuning of both donor and acceptor polymer Mns is critical for optimizing APSC performance. In contrast to reports where maximum power conversion efficiencies (PCEs) are achieved for the highest Mns, the present two-dimensional Mn optimization matrix strategy locates a PCE “sweet spot” at intermediate Mns of both donor and acceptor polymers. This study provides synthetic methodologies to predictably access conjugated polymers with desired Mn and highlights the importance of optimizing Mn for both polymer components to realize the full potential of APSC performance.« less
Andasari, Vivi; Roper, Ryan T.; Swat, Maciej H.; Chaplain, Mark A. J.
2012-01-01
In this paper we present a multiscale, individual-based simulation environment that integrates CompuCell3D for lattice-based modelling on the cellular level and Bionetsolver for intracellular modelling. CompuCell3D or CC3D provides an implementation of the lattice-based Cellular Potts Model or CPM (also known as the Glazier-Graner-Hogeweg or GGH model) and a Monte Carlo method based on the metropolis algorithm for system evolution. The integration of CC3D for cellular systems with Bionetsolver for subcellular systems enables us to develop a multiscale mathematical model and to study the evolution of cell behaviour due to the dynamics inside of the cells, capturing aspects of cell behaviour and interaction that is not possible using continuum approaches. We then apply this multiscale modelling technique to a model of cancer growth and invasion, based on a previously published model of Ramis-Conde et al. (2008) where individual cell behaviour is driven by a molecular network describing the dynamics of E-cadherin and -catenin. In this model, which we refer to as the centre-based model, an alternative individual-based modelling technique was used, namely, a lattice-free approach. In many respects, the GGH or CPM methodology and the approach of the centre-based model have the same overall goal, that is to mimic behaviours and interactions of biological cells. Although the mathematical foundations and computational implementations of the two approaches are very different, the results of the presented simulations are compatible with each other, suggesting that by using individual-based approaches we can formulate a natural way of describing complex multi-cell, multiscale models. The ability to easily reproduce results of one modelling approach using an alternative approach is also essential from a model cross-validation standpoint and also helps to identify any modelling artefacts specific to a given computational approach. PMID:22461894
Ohya, Y.; Botstein, D.
1994-01-01
Conditional-lethal mutations of the single calmodulin gene in Saccharomyces cerevisiae have been very difficult to isolate by random and systematic methods, despite the fact that deletions cause recessive lethality. We report here the isolation of numerous conditional-lethal mutants that were recovered by systematically altering phenylalanine residues. The phenylalanine residues of calmodulin were implicated in function both by structural studies of calmodulin bound to target peptides and by their extraordinary conservation in evolution. Seven single and 26 multiple Phe -> Ala mutations were constructed. Mutant phenotypes were examined in a haploid cmd1 disrupted strain under three conditions: single copy, low copy, and overexpressed. Whereas all but one of the single mutations caused no obvious phenotype, most of the multiple mutations caused obvious growth phenotypes. Five were lethal, 6 were lethal only in synthetic medium, 13 were temperature-sensitive lethal and 2 had no discernible phenotypic consequences. Overexpression of some of the mutant genes restored the phenotype to nearly wild type. Several temperature-sensitive calmodulin mutations were suppressed by elevated concentration of CaCl(2) in the medium. Mutant calmodulin protein was detected at normal levels in extracts of most of the lethal mutant cells, suggesting that the deleterious phenotypes were due to loss of the calmodulin function and not protein instability. Analysis of diploid strains heterozygous for all combinations of cmd1-ts alleles revealed four intragenic complementation groups. The contributions of individual phe->ala changes to mutant phenotypes support the idea of internal functional redundancy in the symmetrical calmodulin protein molecule. These results suggest that the several phenylalanine residues in calmodulin are required to different extents in different combinations in order to carry out each of the several essential tasks. PMID:7896089
Kimoto, Michiko; Nakamura, Mana; Hirao, Ichiro
2016-09-06
A new technology, genetic alphabet expansion using artificial bases (unnatural bases), has created high-affinity DNA ligands (aptamers) that specifically bind to target proteins by ExSELEX (genetic alphabet Expansion for Systematic Evolution of Ligands by EXponential enrichment). We recently found that the unnatural-base DNA aptamers can be stabilized against nucleases, by introducing an extraordinarily stable, unique hairpin DNA (mini-hairpin DNA) and by reinforcing the stem region with G-C pairs. Here, to establish this aptamer generation method, we examined the stabilization of a high-affinity anti-VEGF165 unnatural-base DNA aptamer. The stabilized aptamers displayed significantly increased thermal and nuclease stabilities, and furthermore, exhibited higher affinity to the target. As compared to the well-known anti-VEGF165 RNA aptamer, pegaptanib (Macugen), our aptamers did not require calcium ions for binding to VEGF165 Biological experiments using cultured cells revealed that our stabilized aptamers efficiently inhibited the interaction between VEGF165 and its receptor, with the same or slightly higher efficiency than that of the pegaptanib RNA aptamer. The development of cost-effective and calcium ion-independent high-affinity anti-VEGF165 DNA aptamers encourages further progress in diagnostic and therapeutic applications. In addition, the stabilization process provided additional information about the key elements required for aptamer binding to VEGF165. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Setyawan, Wahyu; Nandipati, Giridhar; Kurtz, Richard J.
The stability of tungsten self-interstitial atom (SIA) clusters is studied using first-principles methods. Clusters from one to seven SIAs are systematically explored from 1264 unique configurations. Finite-size effect of the simulation cell is corrected based on the scaling of formation energy versus inverse volume cell. Furthermore, the accuracy of the calculations is improved by treating the 5p semicore states as valence states. Configurations of the three most stable clusters in each cluster size n are presented, which consist of parallel [111] dumbbells. The evolution of these clusters leading to small dislocation loops is discussed. The binding energy of size-n clustersmore » is analyzed relative to an n → (n-1) + 1 dissociation and is shown to increase with size. Extrapolation for n > 7 is presented using a dislocation loop model. In addition, the interaction of these clusters with a substitutional Re, Os, or Ta solute is explored by replacing one of the dumbbells with the solute. Re and Os strongly attract these clusters, but Ta strongly repels. The strongest interaction is found when the solute is located on the periphery of the cluster rather than in the middle. The magnitude of this interaction decreases with cluster size. Empirical fits to describe the trend of the solute binding energy are presented.« less
Cell–cell signaling drives the evolution of complex traits: introduction—lung evo-devo
Torday, John S.; Rehan, V. K.
2009-01-01
Physiology integrates biology with the environment through cell–cell interactions at multiple levels. The evolution of the respiratory system has been “deconvoluted” (Torday and Rehan in Am J Respir Cell Mol Biol 31:8–12, 2004) through Gene Regulatory Networks (GRNs) applied to cell–cell communication for all aspects of lung biology development, homeostasis, regeneration, and aging. Using this approach, we have predicted the phenotypic consequences of failed signaling for lung development, homeostasis, and regeneration based on evolutionary principles. This cell–cell communication model predicts other aspects of vertebrate physiology as adaptational responses. For example, the oxygen-induced differentiation of alveolar myocytes into alveolar adipocytes was critical for the evolution of the lung in land dwelling animals adapting to fluctuating Phanarezoic oxygen levels over the past 500 million years. Adipocytes prevent lung injury due to oxygen radicals and facilitate the rise of endothermy. In addition, they produce the class I cytokine leptin, which augments pulmonary surfactant activity and alveolar surface area, increasing selection pressure for both respiratory oxygenation and metabolic demand initially constrained by high-systemic vascular pressure, but subsequently compensated by the evolution of the adrenomedullary beta-adrenergic receptor mechanism. Conserted positive selection for the lung and adrenals created further selection pressure for the heart, which becomes progressively more complex phylogenetically in tandem with the lung. Developmentally, increasing heart complexity and size impinges precociously on the gut mesoderm to induce the liver. That evolutionary-developmental interaction is significant because the liver provides regulated sources of glucose and glycogen to the evolving physiologic system, which is necessary for the evolution of the neocortex. Evolution of neocortical control furthers integration of physiologic systems. Such an evolutionary vertical integration of cell-to-tissue-to-organ-to-physiology of intrinsic cell–cell signaling and extrinsic factors is the reverse of the “top-down” conventional way in which physiologic systems are usually regarded. This novel mechanistic approach, incorporating a “middle-out” cell–cell signaling component, will lead to a readily available algorithm for integrating genes and phenotypes. This symposium surveyed the phylogenetic origins of such vertically integrated mechanisms for the evolution of cell–cell communication as the basis for complex physiologic traits, from sponges to man. PMID:20607136
A conceptual framework for the evolutionary origins of multicellularity
NASA Astrophysics Data System (ADS)
Libby, Eric; Rainey, Paul B.
2013-06-01
The evolution of multicellular organisms from unicellular counterparts involved a transition in Darwinian individuality from single cells to groups. A particular challenge is to understand the nature of the earliest groups, the causes of their evolution, and the opportunities for emergence of Darwinian properties. Here we outline a conceptual framework based on a logical set of possible pathways for evolution of the simplest self-replicating groups. Central to these pathways is the recognition of a finite number of routes by which genetic information can be transmitted between individual cells and groups. We describe the form and organization of each primordial group state and consider factors affecting persistence and evolution of the nascent multicellular forms. Implications arising from our conceptual framework become apparent when attempting to partition fitness effects at individual and group levels. These are discussed with reference to the evolutionary emergence of individuality and its manifestation in extant multicellular life—including those of marginal Darwinian status.
Shen, Chen; Chu, Chen; Shi, Lei
2018-01-01
In this article, we propose an aspiration-based coevolution of link weight, and explore how this set-up affects the evolution of cooperation in the spatial prisoner's dilemma game. In particular, an individual will increase the weight of its link to its neighbours only if the payoff received via this interaction exceeds a pre-defined aspiration. Conversely, if the received payoff is below this aspiration, the link weight with the corresponding neighbour will decrease. Our results show that an appropriate aspiration level leads to a high-cooperation plateau, whereas too high or too low aspiration will impede the evolution of cooperation. We explain these findings with a comprehensive analysis of transition points and with a systematic analysis of typical configuration patterns. The presented results provide further theoretical insights with regards to the impact of different aspiration levels on cooperation in human societies. PMID:29892454
NASA Astrophysics Data System (ADS)
Shen, Chen; Chu, Chen; Shi, Lei; Perc, Matjaž; Wang, Zhen
2018-05-01
In this article, we propose an aspiration-based coevolution of link weight, and explore how this set-up affects the evolution of cooperation in the spatial prisoner's dilemma game. In particular, an individual will increase the weight of its link to its neighbours only if the payoff received via this interaction exceeds a pre-defined aspiration. Conversely, if the received payoff is below this aspiration, the link weight with the corresponding neighbour will decrease. Our results show that an appropriate aspiration level leads to a high-cooperation plateau, whereas too high or too low aspiration will impede the evolution of cooperation. We explain these findings with a comprehensive analysis of transition points and with a systematic analysis of typical configuration patterns. The presented results provide further theoretical insights with regards to the impact of different aspiration levels on cooperation in human societies.
Evolution of the Valley Position in Bulk Transition-Metal Chalcogenides and Their Monolayer Limit
Yuan, Hongtao; Liu, Zhongkai; Xu, Gang; ...
2016-07-12
Valley physics based on layered transition metal chalcogenides have recently sparked much interest due to their potential spintronics and valleytronics applications. However, most current understanding of the electronic structure near band valleys in momentum space is based on either theoretical investigations or optical measurements, leaving the detailed band structure elusive. For example, the exact position of the conduction band valley of bulk MoS 2 remains controversial. Here, using angle-resolved photoemission spectroscopy with sub-micron spatial resolution (micro- ARPES), we systematically imaged the conduction/valence band structure evolution across representative chalcogenides MoS 2, WS 2 and WSe 2, as well as the thicknessmore » dependent electronic structure from bulk to the monolayer limit. These results establish a solid basis to understand the underlying valley physics of these materials, and also provide a link between chalcogenide electronic band structure and their physical properties for potential valleytronics applications.« less
An Observation-Driven Agent-Based Modeling and Analysis Framework for C. elegans Embryogenesis.
Wang, Zi; Ramsey, Benjamin J; Wang, Dali; Wong, Kwai; Li, Husheng; Wang, Eric; Bao, Zhirong
2016-01-01
With cutting-edge live microscopy and image analysis, biologists can now systematically track individual cells in complex tissues and quantify cellular behavior over extended time windows. Computational approaches that utilize the systematic and quantitative data are needed to understand how cells interact in vivo to give rise to the different cell types and 3D morphology of tissues. An agent-based, minimum descriptive modeling and analysis framework is presented in this paper to study C. elegans embryogenesis. The framework is designed to incorporate the large amounts of experimental observations on cellular behavior and reserve data structures/interfaces that allow regulatory mechanisms to be added as more insights are gained. Observed cellular behaviors are organized into lineage identity, timing and direction of cell division, and path of cell movement. The framework also includes global parameters such as the eggshell and a clock. Division and movement behaviors are driven by statistical models of the observations. Data structures/interfaces are reserved for gene list, cell-cell interaction, cell fate and landscape, and other global parameters until the descriptive model is replaced by a regulatory mechanism. This approach provides a framework to handle the ongoing experiments of single-cell analysis of complex tissues where mechanistic insights lag data collection and need to be validated on complex observations.
Kim, Hyun Seok; Mendiratta, Saurabh; Kim, Jiyeon; Pecot, Chad Victor; Larsen, Jill E.; Zubovych, Iryna; Seo, Bo Yeun; Kim, Jimi; Eskiocak, Banu; Chung, Hannah; McMillan, Elizabeth; Wu, Sherry; De Brabander, Jef; Komurov, Kakajan; Toombs, Jason E.; Wei, Shuguang; Peyton, Michael; Williams, Noelle; Gazdar, Adi F.; Posner, Bruce A.; Brekken, Rolf; Sood, Anil K.; Deberardinis, Ralph J.; Roth, Michael G.; Minna, John D.; White, Michael A.
2013-01-01
SUMMARY Context-specific molecular vulnerabilities that arise during tumor evolution represent an attractive intervention target class. However, the frequency and diversity of somatic lesions detected among lung tumors can confound efforts to identify these targets. To confront this challenge, we have applied parallel screening of chemical and genetic perturbations within a panel of molecularly annotated NSCLC lines to identify intervention opportunities tightly linked to molecular response indicators predictive of target sensitivity. Anchoring this analysis on a matched tumor/normal cell model from a lung adenocarcinoma patient identified three distinct target/response-indicator pairings that are represented with significant frequencies (6–16%) in the patient population. These include NLRP3 mutation/inflammasome activation-dependent FLIP addiction, co-occuring KRAS and LKB1 mutation-driven COPI addiction, and selective sensitivity to a synthetic indolotriazine that is specified by a 7-gene expression signature. Target efficacies were validated in vivo, and mechanism of action studies uncovered new cancer cell biology. PMID:24243015
Kim, Hyun Seok; Mendiratta, Saurabh; Kim, Jiyeon; Pecot, Chad Victor; Larsen, Jill E; Zubovych, Iryna; Seo, Bo Yeun; Kim, Jimi; Eskiocak, Banu; Chung, Hannah; McMillan, Elizabeth; Wu, Sherry; De Brabander, Jef; Komurov, Kakajan; Toombs, Jason E; Wei, Shuguang; Peyton, Michael; Williams, Noelle; Gazdar, Adi F; Posner, Bruce A; Brekken, Rolf A; Sood, Anil K; Deberardinis, Ralph J; Roth, Michael G; Minna, John D; White, Michael A
2013-10-24
Context-specific molecular vulnerabilities that arise during tumor evolution represent an attractive intervention target class. However, the frequency and diversity of somatic lesions detected among lung tumors can confound efforts to identify these targets. To confront this challenge, we have applied parallel screening of chemical and genetic perturbations within a panel of molecularly annotated NSCLC lines to identify intervention opportunities tightly linked to molecular response indicators predictive of target sensitivity. Anchoring this analysis on a matched tumor/normal cell model from a lung adenocarcinoma patient identified three distinct target/response-indicator pairings that are represented with significant frequencies (6%-16%) in the patient population. These include NLRP3 mutation/inflammasome activation-dependent FLIP addiction, co-occurring KRAS and LKB1 mutation-driven COPI addiction, and selective sensitivity to a synthetic indolotriazine that is specified by a seven-gene expression signature. Target efficacies were validated in vivo, and mechanism-of-action studies informed generalizable principles underpinning cancer cell biology. Copyright © 2013 Elsevier Inc. All rights reserved.
ERIC Educational Resources Information Center
Boulabiar, Ahlem; Bouraoui, Kamel; Chastrette, Maurice; Abderrabba, Manef
2004-01-01
The condition in which the Daniell Cell was historically constructed is examined and the evolution of its presentation in French and Tunisian chemistry textbooks is analyzed. Based on the studies, several innovations to facilitate the teaching of the cell, and more generally, the teaching of electrochemistry and of ionic conduction are proposed.
Effects of neutron irradiation on carbon doped MgB2 wire segments
NASA Astrophysics Data System (ADS)
Wilke, R. H. T.; Bud'ko, S. L.; Canfield, P. C.; Finnemore, D. K.; Suplinskas, Raymond J.; Farmer, J.; Hannahs, S. T.
2006-06-01
We have studied the evolution of superconducting and normal state properties of neutron irradiated Mg(B0.962C0.038)2 wire segments as a function of post-exposure annealing time and temperature. The initial fluence fully suppressed superconductivity and resulted in an anisotropic expansion of the unit cell. Superconductivity was restored by post-exposure annealing. The upper critical field, Hc2(T = 0), approximately scales with Tc, starting with an undamaged Tc near 37 K and Hc2(T = 0) near 32 T. Up to an annealing temperature of 400 °C the recovery of Tc tends to coincide with a decrease in the normal state resistivity and a systematic recovery of the lattice parameters. Above 400 °C a decrease in ordering along the c-direction coincides with an increase in resistivity, but no apparent change in the evolution of Tc and Hc2. To a first order approximation, it appears that carbon doping and neutron damage affect the superconducting properties of MgB2 independently.
Velisavljevic, N.; Sinogeikin, S.; Saavedra, R.; ...
2014-05-07
Here, we have designed a portable pressure controller module to tune compression rates and maximum pressures attainable in a standard gas-membrane diamond anvil cell (DAC). During preliminary experiments, performed on zirconium (Zr) metal sample, pressure jumps of up to 80 GPa were systematically obtained in less than 0.2s (resulting in compression rate of few GPa/s up to more than 400 GPa/s). In-situ x-ray diffraction and electrical resistance measurements were performed simultaneously during this rapid pressure increase to provide the first time resolved data on α → ω → β structural evolution in Zr at high pressures. Direct control of compressionmore » rates and peak pressures, which can be held for prolonged time, allows for investigation of structural evolution and kinetics of structural phase transitions of materials under previously unexplored compression rate-pressure conditions that bridge traditional static and shock/dynamic experimental platforms.« less
An Insilico Design of Nanoclay Based Nanocomposites and Scaffolds in Bone Tissue Engineering
NASA Astrophysics Data System (ADS)
Sharma, Anurag
A multiscale in silico approach to design polymer nanocomposites and scaffolds for bone tissue engineering applications is described in this study. This study focuses on the role of biomaterials design and selection, structural integrity and mechanical properties evolution during degradation and tissue regeneration in the successful design of polymer nanocomposite scaffolds. Polymer nanocomposite scaffolds are synthesized using aminoacid modified montmorillonite nanoclay with biomineralized hydroxyapatite and polycaprolactone (PCL/in situ HAPclay). Representative molecular models of polymer nanocomposite system are systematically developed using molecular dynamics (MD) technique and successfully validated using material characterization techniques. The constant force steered molecular dynamics (fSMD) simulation results indicate a two-phase nanomechanical behavior of the polymer nanocomposite. The MD and fSMD simulations results provide quantitative contributions of molecular interactions between different constituents of representative models and their effect on nanomechanical responses of nanoclay based polymer nanocomposite system. A finite element (FE) model of PCL/in situ HAPclay scaffold is built using micro-computed tomography images and bridging the nanomechanical properties obtained from fSMD simulations into the FE model. A new reduction factor, K is introduced into modeling results to consider the effect of wall porosity of the polymer scaffold. The effect of accelerated degradation under alkaline conditions and human osteoblast cells culture on the evolution of mechanical properties of scaffolds are studied and the damage mechanics based analytical models are developed. Finally, the novel multiscale models are developed that incorporate the complex molecular and microstructural properties, mechanical properties at nanoscale and structural levels and mechanical properties evolution during degradation and tissue formation in the polymer nanocomposite scaffold. Overall, this study provides a leap into methodologies for in silico design of biomaterials for bone tissue engineering applications. Furthermore, as a part of this work, a molecular dynamics study of rice DNA in the presence of single walled carbon nanotube is carried out to understand the role played by molecular interactions in the conformation changes of rice DNA. The simulations results showed wrapping of DNA onto SWCNT, breaking and forming of hydrogen bonds due to unzipping of Watson-Crick (WC) nucleobase pairs and forming of new non-WC nucleobase pairs in DNA.
Gedi, Vinayakumar; Kim, Young-Pil
2014-01-01
Detection and characterization of cells using aptamers and aptamer-conjugated nanoprobes has evolved a great deal over the past few decades. This evolution has been driven by the easy selection of aptamers via in vitro cell-SELEX, permitting sensitive discrimination between target and normal cells, which includes pathogenic prokaryotic and cancerous eukaryotic cells. Additionally, when the aptamer-based strategies are used in conjunction with nanomaterials, there is the potential for cell targeting and therapeutic effects with improved specificity and sensitivity. Here we review recent advances in aptamer-based nano-conjugates and their applications for detecting cancer cells and pathogenic bacteria. The multidisciplinary research utilized in this field will play an increasingly significant role in clinical medicine and drug discovery. PMID:25268922
Swat, Maciej H; Thomas, Gilberto L; Shirinifard, Abbas; Clendenon, Sherry G; Glazier, James A
2015-01-01
Tumor cells and structure both evolve due to heritable variation of cell behaviors and selection over periods of weeks to years (somatic evolution). Micro-environmental factors exert selection pressures on tumor-cell behaviors, which influence both the rate and direction of evolution of specific behaviors, especially the development of tumor-cell aggression and resistance to chemotherapies. In this paper, we present, step-by-step, the development of a multi-cell, virtual-tissue model of tumor somatic evolution, simulated using the open-source CompuCell3D modeling environment. Our model includes essential cell behaviors, microenvironmental components and their interactions. Our model provides a platform for exploring selection pressures leading to the evolution of tumor-cell aggression, showing that emergent stratification into regions with different cell survival rates drives the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins. Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors.
Swat, Maciej H.; Thomas, Gilberto L.; Shirinifard, Abbas; Clendenon, Sherry G.; Glazier, James A.
2015-01-01
Tumor cells and structure both evolve due to heritable variation of cell behaviors and selection over periods of weeks to years (somatic evolution). Micro-environmental factors exert selection pressures on tumor-cell behaviors, which influence both the rate and direction of evolution of specific behaviors, especially the development of tumor-cell aggression and resistance to chemotherapies. In this paper, we present, step-by-step, the development of a multi-cell, virtual-tissue model of tumor somatic evolution, simulated using the open-source CompuCell3D modeling environment. Our model includes essential cell behaviors, microenvironmental components and their interactions. Our model provides a platform for exploring selection pressures leading to the evolution of tumor-cell aggression, showing that emergent stratification into regions with different cell survival rates drives the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins. Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors. PMID:26083246
Evolution of pollen morphology in Loranthaceae
Grímsson, Friðgeir; Grimm, Guido W.; Zetter, Reinhard
2018-01-01
Abstract Earlier studies indicate a strong correlation of pollen morphology and ultrastructure with taxonomy in Loranthaceae. Using high-resolution light microscopy and scanning electron microscopy imaging of the same pollen grains, we document pollen types of 35 genera including 15 studied for the first time. Using a molecular phylogenetic framework based on currently available sequence data with good genus-coverage, we reconstruct trends in the evolution of Loranthaceae pollen and pinpoint traits of high diagnostic value, partly confirming earlier intuitive hypotheses based on morphological observations. We find that pollen morphology in Loranthaceae is strongly linked to phylogenetic relationships. Some pollen types are diagnostic for discrete genera or evolutionary lineages, opening the avenue to recruit dispersed fossil pollen as age constraints for dated phylogenies and as independent data for testing biogeographic scenarios; so far based exclusively on modern-day data. Correspondences and discrepancies between palynological and molecular data and current taxonomic/systematic concepts are identified and suggestions made for future palynological and molecular investigations of Loranthaceae. PMID:29386990
NASA Technical Reports Server (NTRS)
Moriwaki, R.; Usui, T.; Simon, J. I.; Jones, J. H.; Yokoyama, T.
2015-01-01
Geochemically-depleted shergottites are basaltic rocks derived from a martian mantle source reservoir. Geochemical evolution of the martian mantle has been investigated mainly based on the Rb-Sr, Sm-Nd, and Lu-Hf isotope systematics of the shergottites [1]. Although potentially informative, U-Th- Pb isotope systematics have been limited because of difficulties in interpreting the analyses of depleted meteorite samples that are more susceptible to the effects of near-surface processes and terrestrial contamination. This study conducts a 5-step sequential acid leaching experiment of the first witnessed fall of the geochemically-depleted olivinephyric shergottite Tissint to minimize the effect of low temperature distrubence. Trace element analyses of the Tissint acid residue (mostly pyroxene) indicate that Pb isotope compositions of the residue do not contain either a martian surface or terrestrial component, but represent the Tissint magma source [2]. The residue has relatively unradiogenic initial Pb isotopic compositions (e.g., 206Pb/204Pb = 10.8136) that fall within the Pb isotope space of other geochemically-depleted shergottites. An initial µ-value (238U/204Pb = 1.5) of Tissint at the time of crystallization (472 Ma [3]) is similar to a time-integrated mu- value (1.72 at 472 Ma) of the Tissint source mantle calculated based on the two-stage mantle evolution model [1]. On the other hand, the other geochemically-depleted shergottites (e.g., QUE 94201 [4]) have initial µ-values of their parental magmas distinctly lower than those of their modeled source mantle. These results suggest that only Tissint potentially reflects the geochemical signature of the shergottite mantle source that originated from cumulates of the martian magma ocean
Sun, Bian Na; Wei, Luan Luan; Shen, He Ding; Wu, Hong Xi; Wang, Dong Feng
2016-09-01
We generated complete mitochondrial genome sequences data for 4 genera (Onchidium, Platevindex, Paraoncidium and Peronia) in Onchidiidae to construct a phylogenetic tree in conjunction with other 9 existing data among gastropods. The topology showed that the taxa clustered into two main groups of four species, one of which included Onchidium struma and the Platevindex mortoni, the other Paraoncidium reevesii and Peronia verruculata. The process in Pulmonata from sea to land in accordance with the evolution of respiratory organs from branchial gills to pulmonary cavity has been shown. This will also constitute a framework for phylogeny evolution analysis, systematic classfication of Onchidiidae and other euthyneurans (pulmonates and opisthobranchs).
NASA Astrophysics Data System (ADS)
Britavskiy, N.; Bonanos, A. Z.; Mehner, A.
2015-01-01
We present the first systematic survey of dusty massive stars (RSGs, LBVs, sgB[e]) in nearby galaxies, with the goal of understanding their importance in massive star evolution. Using the fact that these stars are bright in mid-infrared colors due to dust, we provide a technique for selecting and identifying dusty evolved stars based on the results of Bonanos et al. (2009, 2010), Britavskiy et al. (2014), and archival Spitzer/IRAC photometry. We present the results of our spectroscopic follow-up of luminous infrared sources in the Local Group dwarf irregular galaxies: Pegasus, Phoenix, Sextans A and WLM. The survey aims to complete the census of dusty massive stars in the Local Group.
Identification of liver cancer-specific aptamers using whole live cells.
Shangguan, Dihua; Meng, Ling; Cao, Zehui Charles; Xiao, Zeyu; Fang, Xiaohong; Li, Ying; Cardona, Diana; Witek, Rafal P; Liu, Chen; Tan, Weihong
2008-02-01
Liver cancer is the third most deadly cancers in the world. Unfortunately, there is no effective treatment. One of the major problems is that most cancers are diagnosed in the later stage, when surgical resection is not feasible. Thus, accurate early diagnosis would significantly improve the clinical outcome of liver cancer. Currently, there are no effective molecular probes to recognize biomarkers that are specific for liver cancer. The objective of our current study is to identify liver cancer cell-specific molecular probes that could be used for liver cancer recognition and diagnosis. We applied a newly developed cell-SELEX (Systematic Evolution of Ligands by EXponential enrichment) method for the generation of molecular probes for specific recognition of liver cancer cells. The cell-SELEX uses whole live cells as targets to select aptamers (designed DNA/RNA) for cell recognition. In generating aptamers for liver cancer recognition, two liver cell lines were used: a liver cancer cell line BNL 1ME A.7R.1 (MEAR) and a noncancer cell line, BNL CL.2 (BNL). Both cell lines were originally derived from Balb/cJ mice. Through multiple rounds of selection using BNL as a control, we have identified a panel of aptamers that specifically recognize the cancer cell line MEAR with Kd in the nanomolar range. We have also demonstrated that some of the selective aptamers could specifically bind liver cancer cells in a mouse model. There are two major new results (compared with our reported cell-SELEX methodology) in addition to the generation of aptamers specifically for liver cancer. The first one is that our current study demonstrates that cell-based aptamer selection can select specific aptamers for multiple cell lines, even for two cell lines with minor differences (MEAR cell is derived from BNL by chemical inducement); and the second result is that cell-SELEX can be used for adhesive cells and thus open the door for solid tumor selection and investigation. The newly generated cancer-specific aptamers hold great promise as molecular probes for cancer early diagnosis and basic mechanism studies.
Interspecific Plastome Recombination Reflects Ancient Reticulate Evolution in Picea (Pinaceae).
Sullivan, Alexis R; Schiffthaler, Bastian; Thompson, Stacey Lee; Street, Nathaniel R; Wang, Xiao-Ru
2017-07-01
Plastid sequences are a cornerstone in plant systematic studies and key aspects of their evolution, such as uniparental inheritance and absent recombination, are often treated as axioms. While exceptions to these assumptions can profoundly influence evolutionary inference, detecting them can require extensive sampling, abundant sequence data, and detailed testing. Using advancements in high-throughput sequencing, we analyzed the whole plastomes of 65 accessions of Picea, a genus of ∼35 coniferous forest tree species, to test for deviations from canonical plastome evolution. Using complementary hypothesis and data-driven tests, we found evidence for chimeric plastomes generated by interspecific hybridization and recombination in the clade comprising Norway spruce (P. abies) and 10 other species. Support for interspecific recombination remained after controlling for sequence saturation, positive selection, and potential alignment artifacts. These results reconcile previous conflicting plastid-based phylogenies and strengthen the mounting evidence of reticulate evolution in Picea. Given the relatively high frequency of hybridization and biparental plastid inheritance in plants, we suggest interspecific plastome recombination may be more widespread than currently appreciated and could underlie reported cases of discordant plastid phylogenies. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
Bioattractors: dynamical systems theory and the evolution of regulatory processes
Jaeger, Johannes; Monk, Nick
2014-01-01
In this paper, we illustrate how dynamical systems theory can provide a unifying conceptual framework for evolution of biological regulatory systems. Our argument is that the genotype–phenotype map can be characterized by the phase portrait of the underlying regulatory process. The features of this portrait – such as attractors with associated basins and their bifurcations – define the regulatory and evolutionary potential of a system. We show how the geometric analysis of phase space connects Waddington's epigenetic landscape to recent computational approaches for the study of robustness and evolvability in network evolution. We discuss how the geometry of phase space determines the probability of possible phenotypic transitions. Finally, we demonstrate how the active, self-organizing role of the environment in phenotypic evolution can be understood in terms of dynamical systems concepts. This approach yields mechanistic explanations that go beyond insights based on the simulation of evolving regulatory networks alone. Its predictions can now be tested by studying specific, experimentally tractable regulatory systems using the tools of modern systems biology. A systematic exploration of such systems will enable us to understand better the nature and origin of the phenotypic variability, which provides the substrate for evolution by natural selection. PMID:24882812
Establishment of the Vertebrate Germ Layers.
Tseng, Wei-Chia; Munisha, Mumingjiang; Gutierrez, Juan B; Dougan, Scott T
2017-01-01
The process of germ layer formation is a universal feature of animal development. The germ layers separate the cells that produce the internal organs and tissues from those that produce the nervous system and outer tissues. Their discovery in the early nineteenth century transformed embryology from a purely descriptive field into a rigorous scientific discipline, in which hypotheses could be tested by observation and experimentation. By systematically addressing the questions of how the germ layers are formed and how they generate overall body plan, scientists have made fundamental contributions to the fields of evolution, cell signaling, morphogenesis, and stem cell biology. At each step, this work was advanced by the development of innovative methods of observing cell behavior in vivo and in culture. Here, we take an historical approach to describe our current understanding of vertebrate germ layer formation as it relates to the long-standing questions of developmental biology. By comparing how germ layers form in distantly related vertebrate species, we find that highly conserved molecular pathways can be adapted to perform the same function in dramatically different embryonic environments.
Legionella pathogenicity: genome structure, regulatory networks and the host cell response.
Steinert, Michael; Heuner, Klaus; Buchrieser, Carmen; Albert-Weissenberger, Christiane; Glöckner, Gernot
2007-11-01
Legionella spp. the causative agent of Legionnaires' disease is naturally found in fresh water where the bacteria parasitize intracellularly within protozoa. Upon aerosol formation via man-made water systems, Legionella can enter the human lung and cause a severe form of pneumonia. Here we review results from systematic comparative genome analysis of Legionella species with different pathogenic potentials. The complete genomes reveal that horizontal gene transfer has played an important role during the evolution of Legionella and indicate the importance of secretion machineries for the intracellular lifestyle of this pathogen. Moreover, we highlight recent findings on the in vivo transcriptional program of L. pneumophila and the regulatory networks involved in the biphasic life cycle. In order to understand how Legionella effectively subvert host cell functions for its own benefit the transcriptional host cell response upon infection of the model amoeba Dictyostelium discoideum was studied. The use of this model organism made it possible to develop a roadmap of host cell factors which significantly contribute to the uptake of L. pneumophila and the establishment of an ER-associated replicative vacuole.
Fuel Cells | Hydrogen and Fuel Cells | NREL
Reduction Reaction for Ultrathin Uniform Pt/C Catalyst Layers without Influence from Nafion, Electrochimica Acta (2016) Suppression of Oxygen Reduction Reaction Activity on Pt-Based Electrocatalysts from Ionomer Durability of Iridium Nanoparticles in the Oxygen Evolution Reaction, Journal of the Electrochemical Society
NASA Astrophysics Data System (ADS)
Clairambault, Jean
2016-06-01
This session investigates hot topics related to mathematical representations of cell and cell population dynamics in biology and medicine, in particular, but not only, with applications to cancer. Methods in mathematical modelling and analysis, and in statistical inference using single-cell and cell population data, should contribute to focus this session on heterogeneity in cell populations. Among other methods are proposed: a) Intracellular protein dynamics and gene regulatory networks using ordinary/partial/delay differential equations (ODEs, PDEs, DDEs); b) Representation of cell population dynamics using agent-based models (ABMs) and/or PDEs; c) Hybrid models and multiscale models to integrate single-cell dynamics into cell population behaviour; d) Structured cell population dynamics and asymptotic evolution w.r.t. relevant traits; e) Heterogeneity in cancer cell populations: origin, evolution, phylogeny and methods of reconstruction; f) Drug resistance as an evolutionary phenotype: predicting and overcoming it in therapeutics; g) Theoretical therapeutic optimisation of combined drug treatments in cancer cell populations and in populations of other organisms, such as bacteria.
Orthonectids Are Highly Degenerate Annelid Worms.
Schiffer, Philipp H; Robertson, Helen E; Telford, Maximilian J
2018-05-24
The animal groups of Orthonectida and Dicyemida are tiny, extremely simple, vermiform endoparasites of various marine animals and have been linked in the Mesozoa (Figure 1). The Orthonectida (Figures 1A and 1B) have a few hundred cells, including a nervous system of just ten cells [2], and the Dicyemida (Figure 1C) are even simpler, with ∼40 cells [3]. They are classic "Problematica" [4]-the name Mesozoa suggests an evolutionary position intermediate between Protozoa and Metazoa (animals) [5] and implies that their simplicity is a primitive state, but molecular data have shown they are members of Lophotrochozoa within Bilateria [6-9], which means that they derive from a more complex ancestor. Their precise affinities remain uncertain, however, and it is disputed whether they even constitute a clade. Ascertaining their affinities is complicated by the very fast evolution observed in their genes, potentially leading to the common systematic error of long-branch attraction (LBA) [10]. Here, we use mitochondrial and nuclear gene sequence data and show that both dicyemids and orthonectids are members of the Lophotrochozoa. Carefully addressing the effects of unequal rates of evolution, we show that the Mesozoa is polyphyletic. While the precise position of dicyemids remains unresolved within Lophotrochozoa, we identify orthonectids as members of the phylum Annelida. This result reveals one of the most extreme cases of body-plan simplification in the animal kingdom; our finding makes sense of an annelid-like cuticle in orthonectids [2] and suggests that the circular muscle cells repeated along their body [11] may be segmental in origin. Copyright © 2018 Elsevier Ltd. All rights reserved.
Poissant, Jocelyn; Wilson, Alastair J; Coltman, David W
2010-01-01
The independent evolution of the sexes may often be constrained if male and female homologous traits share a similar genetic architecture. Thus, cross-sex genetic covariance is assumed to play a key role in the evolution of sexual dimorphism (SD) with consequent impacts on sexual selection, population dynamics, and speciation processes. We compiled cross-sex genetic correlations (r(MF)) estimates from 114 sources to assess the extent to which the evolution of SD is typically constrained and test several specific hypotheses. First, we tested if r(MF) differed among trait types and especially between fitness components and other traits. We also tested the theoretical prediction of a negative relationship between r(MF) and SD based on the expectation that increases in SD should be facilitated by sex-specific genetic variance. We show that r(MF) is usually large and positive but that it is typically smaller for fitness components. This demonstrates that the evolution of SD is typically genetically constrained and that sex-specific selection coefficients may often be opposite in sign due to sub-optimal levels of SD. Most importantly, we confirm that sex-specific genetic variance is an important contributor to the evolution of SD by validating the prediction of a negative correlation between r(MF) and SD.
Ojosnegros, Samuel; Beerenwinkel, Niko; Domingo, Esteban
2010-07-01
A single and purified clone of foot-and-mouth disease virus diversified in cell culture into two subpopulations that were genetically distinct. The subpopulation with higher virulence was a minority and was suppressed by the dominant but less virulent one. These two populations follow the competitioncolonization dynamics described in ecology. Virulent viruses can be regarded as colonizers because they killed the cells faster and they spread faster. The attenuated subpopulation resembles competitors because of its higher replication efficiency in coinfected cells. Our results suggest a new model for the evolution of virulence which is based on interactions between components of the quasispecies. Competition between viral mutants takes place at two levels, intracellular competition and competition for new cells. The two strategies are subjected to densitydependent selection.
Stability and bifurcation in a model for the dynamics of stem-like cells in leukemia under treatment
NASA Astrophysics Data System (ADS)
Rǎdulescu, I. R.; Cândea, D.; Halanay, A.
2012-11-01
A mathematical model for the dynamics of leukemic cells during treatment is introduced. Delay differential equations are used to model cells' evolution and are based on the Mackey-Glass approach, incorporating Goldie-Coldman law. Since resistance is propagated by cells that have the capacity of self-renewal, a population of stem-like cells is studied. Equilibrium points are calculated and their stability properties are investigated.
Gas Evolution in Operating Lithium-Ion Batteries Studied In Situ by Neutron Imaging
Michalak, Barbara; Sommer, Heino; Mannes, David; Kaestner, Anders; Brezesinski, Torsten; Janek, Jürgen
2015-01-01
Gas generation as a result of electrolyte decomposition is one of the major issues of high-performance rechargeable batteries. Here, we report the direct observation of gassing in operating lithium-ion batteries using neutron imaging. This technique can be used to obtain qualitative as well as quantitative information by applying a new analysis approach. Special emphasis is placed on high voltage LiNi0.5Mn1.5O4/graphite pouch cells. Continuous gassing due to oxidation and reduction of electrolyte solvents is observed. To separate gas evolution reactions occurring on the anode from those associated with the cathode interface and to gain more insight into the gassing behavior of LiNi0.5Mn1.5O4/graphite cells, neutron experiments were also conducted systematically on other cathode/anode combinations, including LiFePO4/graphite, LiNi0.5Mn1.5O4/Li4Ti5O12 and LiFePO4/Li4Ti5O12. In addition, the data were supported by gas pressure measurements. The results suggest that metal dissolution in the electrolyte and decomposition products resulting from the high potentials adversely affect the gas generation, particularly in the first charge cycle (i.e., during graphite solid-electrolyte interface layer formation). PMID:26496823
2014-09-30
existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this...through downscaling future projection simulations. APPROACH To address the scientific objectives, we plan to develop, implement, and validate a...ITD and FSD at the same time. The development of MIZMAS will be based on systematic model parameterization, calibration, and validation, and data
Performance benchmarking of four cell-free protein expression systems.
Gagoski, Dejan; Polinkovsky, Mark E; Mureev, Sergey; Kunert, Anne; Johnston, Wayne; Gambin, Yann; Alexandrov, Kirill
2016-02-01
Over the last half century, a range of cell-free protein expression systems based on pro- and eukaryotic organisms have been developed and have found a range of applications, from structural biology to directed protein evolution. While it is generally accepted that significant differences in performance among systems exist, there is a paucity of systematic experimental studies supporting this notion. Here, we took advantage of the species-independent translation initiation sequence to express and characterize 87 N-terminally GFP-tagged human cytosolic proteins of different sizes in E. coli, wheat germ (WGE), HeLa, and Leishmania-based (LTE) cell-free systems. Using a combination of single-molecule fluorescence spectroscopy, SDS-PAGE, and Western blot analysis, we assessed the expression yields, the fraction of full-length translation product, and aggregation propensity for each of these systems. Our results demonstrate that the E. coli system has the highest expression yields. However, we observe that high expression levels are accompanied by production of truncated species-particularly pronounced in the case of proteins larger than 70 kDa. Furthermore, proteins produced in the E. coli system display high aggregation propensity, with only 10% of tested proteins being produced in predominantly monodispersed form. The WGE system was the most productive among eukaryotic systems tested. Finally, HeLa and LTE show comparable protein yields that are considerably lower than the ones achieved in the E. coli and WGE systems. The protein products produced in the HeLa system display slightly higher integrity, whereas the LTE-produced proteins have the lowest aggregation propensity among the systems analyzed. The high quality of HeLa- and LTE-produced proteins enable their analysis without purification and make them suitable for analysis of multi-domain eukaryotic proteins. © 2015 Wiley Periodicals, Inc.
Fritzsch, Bernd; Straka, Hans
2014-01-01
Among the major distance senses of vertebrates, the ear is unique in its complex morphological changes during evolution. Conceivably, these changes enable the ear to adapt toward sensing various physically well-characterized stimuli. This review develops a scenario that integrates sensory cell with organ evolution. We propose that molecular and cellular evolution of the vertebrate hair cells occurred prior to the formation of the vertebrate ear. We previously proposed that the genes driving hair cell differentiation, were aggregated in the otic region through developmental re-patterning that generated a unique vertebrate embryonic structure, the otic placode. In agreement with the presence of graviceptive receptors in many vertebrate outgroups, it is likely that the vertebrate ear originally functioned as a simple gravity-sensing organ. Based on the rare occurrence of angular acceleration receptors in vertebrate outgroups, we further propose that the canal system evolved with a more sophisticated ear morphogenesis. This evolving morphogenesis obviously turned the initial otocyst into a complex set of canals and recesses, harboring multiple sensory epithelia each adapted to the acquisition of a specific aspect of a given physical stimulus. As support for this evolutionary progression, we provide several details of the molecular basis of ear development. PMID:24281353
Isolation and characterization of high affinity aptamers against DNA polymerase iota.
Lakhin, Andrei V; Kazakov, Andrei A; Makarova, Alena V; Pavlov, Yuri I; Efremova, Anna S; Shram, Stanislav I; Tarantul, Viacheslav Z; Gening, Leonid V
2012-02-01
Human DNA-polymerase iota (Pol ι) is an extremely error-prone enzyme and the fidelity depends on the sequence context of the template. Using the in vitro systematic evolution of ligands by exponential enrichment (SELEX) procedure, we obtained an oligoribonucleotide with a high affinity to human Pol ι, named aptamer IKL5. We determined its dissociation constant with homogenous preparation of Pol ι and predicted its putative secondary structure. The aptamer IKL5 specifically inhibits DNA-polymerase activity of the purified enzyme Pol ι, but did not inhibit the DNA-polymerase activities of human DNA polymerases beta and kappa. IKL5 suppressed the error-prone DNA-polymerase activity of Pol ι also in cellular extracts of the tumor cell line SKOV-3. The aptamer IKL5 is useful for studies of the biological role of Pol ι and as a potential drug to suppress the increase of the activity of this enzyme in malignant cells.
Stem cells in bone diseases: current clinical practice.
Beyth, Shaul; Schroeder, Josh; Liebergall, Meir
2011-01-01
Bone is an obvious candidate tissue for stem cell therapy. This review provides an update of existing stem cell-based clinical treatments for bone pathologies. A systematic computerized literature search was conducted. The following databases were accessed on 10 February 2011: NIH clinical trials database, PubMed, Ovid and Cochrane Reviews. Stem cell therapy offers new options for bone conditions, both acquired and inherited. There is still no agreement on the exact definition of 'mesenchymal stem cells'. Consequently, it is difficult to appreciate the effect of culture expansion and the feasibility of allogeneic transplantation. Based on the sound foundations of pre-clinical research, stem cell-based treatments and protocols have recently emerged. Well-designed prospective clinical trials are needed in order to establish and develop stem cell therapy for bone diseases.
The Formation and Early Evolution of Embedded Massive Star Clusters
NASA Astrophysics Data System (ADS)
Barnes, Peter
We propose to combine Spitzer, WISE, Herschel, and other archival spacecraft data with an existing ground- and space-based mm-wave to near-IR survey of molecular clouds over a large portion of the Milky Way, in order to systematically study the formation and early evolution of massive stars and star clusters, and provide new observational calibrations for a theoretical paradigm of this key astrophysical problem. Central Objectives: The Galactic Census of High- and Medium-mass Protostars (CHaMP) is a large, unbiased, uniform, and panchromatic survey of massive star and cluster formation and early evolution, covering 20°x6° of the Galactic Plane. Its uniqueness lies in the comprehensive molecular spectroscopy of 303 massive dense clumps, which have also been included in several archival spacecraft surveys. Our objective is a systematic demographic analysis of massive star and cluster formation, one which has not been possible without knowledge of our CHaMP cloud sample, including all clouds with embedded clusters as well as those that have not yet formed massive stars. For proto-clusters deeply embedded within dense molecular clouds, analysis of these space-based data will: 1. Yield a complete census of Young Stellar Objects in each cluster. 2. Allow systematic measurements of embedded cluster properties: spectral energy distributions, luminosity functions, protostellar and disk fractions, and how these vary with cluster mass, age, and density. Combined with other, similarly complete and unbiased infrared and mm data, CHaMP's goals include: 3. A detailed comparison of the embedded stellar populations with their natal dense gas to derive extinction maps, star formation efficiencies and feedback effects, and the kinematics, physics, and chemistry of the gas in and around the clusters. 4. Tying the demographics, age spreads, and timescales of the clusters, based on pre-Main Sequence evolution, to that of the dense gas clumps and Giant Molecular Clouds. 5. A measurement of the local star formation rate per gas mass surface density in the Milky Way, as well as examining arm versus interarm dependencies. Methods and Techniques: We will primarily use archival cryogenic-Spitzer, WISE, and Herschel data, and support this with existing data from ground- and space-based facilities, to conduct a comprehensive assay of critical metrics (as above) and provide observational calibration of theoretical models over the entire massive star formation process. The mm-wave molecular maps of 303 dense gas clumps in multiple species, comprising all the gas above a column density limit of 100 Msun/pc^2, are already inhand. We have also surveyed the embedded stellar content of these clumps, down to subsolar masses, in the near-infrared J, H, and K bands and with deep Warm Spitzer data. Relevance to NASA programs: Analysis to date of the space- and ground-based data has yielded several new insights into evolutionary timescales and the chemical & energy evolution of clumps during the cluster formation process. Investigations as described in this proposal will yield new demographic insights on how the properties and evolution of molecular clouds relate to the properties of massive stars and clusters that form within them, and significantly enhance the science return from these spacecraft missions. The large number of resulting data products are already being made publicly available to the astronomical community, providing crucial information for future NASA science targets. This research will be performed within the framework of a broad international collaboration spanning four continents. This ambitious but practical program will therefore maximise the science payoff from these archival data sets, provide enhanced legacy data for more advanced studies with the next generation of ground- and space-based instruments such as JWST, and open up several new windows into the discovery space of Galactic star formation & interstellar medium studies.
Directed evolution of cell size in Escherichia coli.
Yoshida, Mari; Tsuru, Saburo; Hirata, Naoko; Seno, Shigeto; Matsuda, Hideo; Ying, Bei-Wen; Yomo, Tetsuya
2014-12-17
In bacteria, cell size affects chromosome replication, the assembly of division machinery, cell wall synthesis, membrane synthesis and ultimately growth rate. In addition, cell size can also be a target for Darwinian evolution for protection from predators. This strong coupling of cell size and growth, however, could lead to the introduction of growth defects after size evolution. An important question remains: can bacterial cell size change and/or evolve without imposing a growth burden? The directed evolution of particular cell sizes, without a growth burden, was tested with a laboratory Escherichia coli strain. Cells of defined size ranges were collected by a cell sorter and were subsequently cultured. This selection-propagation cycle was repeated, and significant changes in cell size were detected within 400 generations. In addition, the width of the size distribution was altered. The changes in cell size were unaccompanied by a growth burden. Whole genome sequencing revealed that only a few mutations in genes related to membrane synthesis conferred the size evolution. In conclusion, bacterial cell size could evolve, through a few mutations, without growth reduction. The size evolution without growth reduction suggests a rapid evolutionary change to diverse cell sizes in bacterial survival strategies.
Moon, Jihea; Kim, Giyoung; Lee, Sangdae; Park, Saetbyeol
2013-11-01
Conventional methods for detection of infective organisms, such as Salmonella, are complicated and require multiple steps, and the need for rapid detection has increased. Biosensors show great potential for rapid detection of pathogens. In turn, aptamers have great potential for biosensor assay development, given their small size, ease of synthesis and labeling, lack of immunogenicity, a lower cost of production than antibodies, and high target specificity. In this study, ssDNA aptamers specific to Salmonella Typhimurium were obtained by a whole bacterium-based systematic evolution of ligands by exponential enrichment (SELEX) procedure and applied to probing S. Typhimurium. After 10 rounds of selection with S. Typhimurium as the target and Salmonella Enteritidis, Escherichia coli and Staphylococcus aureus as counter targets, the highly enriched oligonucleic acid pool was sorted using flow cytometry. In total, 12 aptamer candidates from different families were sequenced and grouped. Fluorescent analysis demonstrated that aptamer C4 had particularly high binding affinity and selectivity; this aptamer was then further characterized. © 2013 Elsevier B.V. All rights reserved.
Eulberg, Dirk; Buchner, Klaus; Maasch, Christian; Klussmann, Sven
2005-01-01
We have developed an automated SELEX (Systematic Evolution of Ligands by EXponential Enrichment) process that allows the execution of in vitro selection cycles without any direct manual intervention steps. The automated selection protocol is designed to provide for high flexibility and versatility in terms of choice of buffers and reagents as well as stringency of selection conditions. Employing the automated SELEX process, we have identified RNA aptamers to the mirror-image configuration (d-peptide) of substance P. The peptide substance P belongs to the tachykinin family and exerts various biologically important functions, such as peripheral vasodilation, smooth muscle contraction and pain transmission. The aptamer that was identified most frequently was truncated to the 44mer SUP-A-004. The mirror-image configuration of SUP-A-004, the so-called Spiegelmer, has been shown to bind to naturally occurring l-substance P displaying a Kd of 40 nM and to inhibit (IC50 of 45 nM) l-substance P-mediated Ca2+ release in a cell culture assay. PMID:15745995
Eulberg, Dirk; Buchner, Klaus; Maasch, Christian; Klussmann, Sven
2005-03-03
We have developed an automated SELEX (Systematic Evolution of Ligands by EXponential Enrichment) process that allows the execution of in vitro selection cycles without any direct manual intervention steps. The automated selection protocol is designed to provide for high flexibility and versatility in terms of choice of buffers and reagents as well as stringency of selection conditions. Employing the automated SELEX process, we have identified RNA aptamers to the mirror-image configuration (d-peptide) of substance P. The peptide substance P belongs to the tachykinin family and exerts various biologically important functions, such as peripheral vasodilation, smooth muscle contraction and pain transmission. The aptamer that was identified most frequently was truncated to the 44mer SUP-A-004. The mirror-image configuration of SUP-A-004, the so-called Spiegelmer, has been shown to bind to naturally occurring l-substance P displaying a K(d) of 40 nM and to inhibit (IC50 of 45 nM) l-substance P-mediated Ca2+ release in a cell culture assay.
Mialdun, A; Ryzhkov, I I; Melnikov, D E; Shevtsova, V
2008-08-22
We report experimental evidence of convection caused by translational vibration of nonuniformly heated fluid in low gravity. The theory of vibrational convection in weightlessness is well developed but direct experimental proof has been missing. An innovative point of the experiment is the observation of a temperature field in the front and side views of the cubic cell. In addition, particle tracing is employed. The evolution of this field is studied systematically in a wide range of frequencies and amplitudes. The flow structures reported in previous numerical studies are confirmed. The transition from four-vortex flow to the pattern with three vortices is observed in the transient state.
Ramamoorthi, Murali; Bakkar, Mohammed; Jordan, Jack; Tran, Simon D.
2015-01-01
Background and Objective. Dental stem cell-based tissue engineered constructs are emerging as a promising alternative to autologous bone transfer for treating bone defects. The purpose of this review is to systematically assess the preclinical in vivo and in vitro studies which have evaluated the efficacy of dental stem cells on bone regeneration. Methods. A literature search was conducted in Ovid Medline, Embase, PubMed, and Web of Science up to October 2014. Implantation of dental stem cells in animal models for evaluating bone regeneration and/or in vitro studies demonstrating osteogenic potential of dental stem cells were included. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used to ensure the quality of the search. Modified ARRIVE (Animal research: reporting in invivo experiments) and CONSORT (Consolidated reporting of trials) were used to critically analyze the selected studies. Results. From 1914 citations, 207 full-text articles were screened and 137 studies were included in this review. Because of the heterogeneity observed in the studies selected, meta-analysis was not possible. Conclusion. Both in vivo and in vitro studies indicate the potential use of dental stem cells in bone regeneration. However well-designed randomized animal trials are needed before moving into clinical trials. PMID:26106427
Park, Angela; Barrera-Ramirez, Juliana; Ranasinghe, Indee; Pilon, Sophie; Sy, Richmond; Fergusson, Dean; Allan, David S
2016-06-01
Mesenchymal stromal cells (MSCs) and endothelial progenitor cells (EPCs) are used in cell-based regenerative therapy. HMG CoA reductase inhibitors (statins) appear promising in blocking apoptosis, prolonging progenitor cell survival and improving their capacity to repair organ function. We performed a systematic review of preclinical and clinical studies to clarify whether statins can improve cell-based repair of organ injury. MEDLINE, EMBASE, and PUBMED databases were searched (1947 to June 25, 2013). Controlled clinical and pre-clinical studies were included that evaluated statin therapy used alone or in combination with MSCs or EPCs in patients or animals with organ injury. After screening 771 citations, 100 records underwent full eligibility screening of which 38 studies met eligibility and were included in the review: Studies were grouped into pre-clinical studies that involved statin treatment in combination with cell therapy (18 studies), preclinical studies of statin therapy alone (13 studies) and clinical studies of statin therapy (7 studies). Studies addressed cardiac injury (14 studies), vascular disorders (15 studies), neurologic conditions (8 studies) and bone fractures (1 study). Pre-clinical studies of statins in combination with MSC infusion (15 studies) or EPC therapy (3 studies) were described and despite marked heterogeneity in reporting outcomes of cellular analysis and organ function, all of these cell-based pre-clinical studies reported improved organ recovery with the addition of statin therapy. Moreover, 13 pre-clinical studies involved the administration of a statin drug alone to animals. An increase in EPC number and/or function (no studies of MSCs) was reported in 11 of these studies (85 %) and improved organ function in 12 studies (92 %). We also identified 7 clinical studies and none involved the administration of cells but described an increased number and/or function of EPCs (no studies of MSCs) and improved organ function with statin therapy (1.2-fold to 35-fold improvement over controls) in all 7 studies. Our systematic review provides a foundation of encouraging results that support further study of statins in regenerative therapy to augment the number and/or function of MSCs used in cell-based repair and to augment the number and function of EPCs in vivo to repair damaged tissues. Larger studies are needed to ensure safety and confirm clinical benefits.
Protein and genome evolution in Mammalian cells for biotechnology applications.
Majors, Brian S; Chiang, Gisela G; Betenbaugh, Michael J
2009-06-01
Mutation and selection are the essential steps of evolution. Researchers have long used in vitro mutagenesis, expression, and selection techniques in laboratory bacteria and yeast cultures to evolve proteins with new properties, termed directed evolution. Unfortunately, the nature of mammalian cells makes applying these mutagenesis and whole-organism evolution techniques to mammalian protein expression systems laborious and time consuming. Mammalian evolution systems would be useful to test unique mammalian cell proteins and protein characteristics, such as complex glycosylation. Protein evolution in mammalian cells would allow for generation of novel diagnostic tools and designer polypeptides that can only be tested in a mammalian expression system. Recent advances have shown that mammalian cells of the immune system can be utilized to evolve transgenes during their natural mutagenesis processes, thus creating proteins with unique properties, such as fluorescence. On a more global level, researchers have shown that mutation systems that affect the entire genome of a mammalian cell can give rise to cells with unique phenotypes suitable for commercial processes. This review examines the advances in mammalian cell and protein evolution and the application of this work toward advances in commercial mammalian cell biotechnology.
CHEERS: Chemical enrichment of clusters of galaxies measured using a large XMM-Newton sample
NASA Astrophysics Data System (ADS)
de Plaa, J.; Mernier, F.; Kaastra, J.; Pinto, C.
2017-10-01
The Chemical Enrichment RGS Sample (CHEERS) is aimed to be a sample of the most optimal clusters of galaxies for observation with the Reflection Grating Spectrometer (RGS) aboard XMM-Newton. It consists of 5 Ms of deep cluster observations of 44 objects obtained through a very large program and archival observations. The main goal is to measure chemical abundances in the hot Intra-Cluster Medium (ICM) of clusters to provide constraints on chemical evolution models. Especially the origin and evolution of type Ia supernovae is still poorly known and X-ray observations could contribute to constrain models regarding the SNIa explosion mechanism. Due to the high quality of the data, the uncertainties on the abundances are dominated by systematic effects. By carefully treating each systematic effect, we increase the accuracy or estimate the remaining uncertainty on the measurement. The resulting abundances are then compared to supernova models. In addition, also radial abundance profiles are derived. In the talk, we present an overview of the results that the CHEERS collaboration obtained based on the CHEERS data. We focus on the abundance measurements. The other topics range from turbulence measurements through line broadening to cool gas in groups.
NASA Technical Reports Server (NTRS)
Gose, W. A.
1974-01-01
Numerous studies on the properties of the moon based on Apollo findings and samples are presented. Topics treated include ages of the lunar nearside light plains and maria, orange material in the Sulpicius Gallus formation at the southwestern edge of Mare Serenitatis, impact-induced fractionation in the lunar highlands, igneous rocks from Apollo 16 rake samples, experimental liquid line of descent and liquid immiscibility for basalt 70017, ion microprobe mass analysis of plagioclase from 'non-mare' lunar samples, grain size and the evolution of lunar soils, chemical composition of rocks and soils at Taurus-Littrow, the geochemical evolution of the moon, U-Th-Pb systematics of some Apollo 17 lunar samples and implications for a lunar basin excavation chronology, volatile-element systematics and green glass in Apollo 15 lunar soils, solar wind nitrogen and indigenous nitrogen in Apollo 17 lunar samples, lunar trapped xenon, solar flare and lunar surface process characterization at the Apollo 17 site, and the permanent and induced magnetic dipole moment of the moon. Individual items are announced in this issue.
Systematic Studies using the UCN τ Magneto-Gravitational Trap
NASA Astrophysics Data System (ADS)
Seestrom, Susan; UCNτ Collaboration
2016-09-01
The UCN τ Experiment measures the neutron lifetime using Ultracold Neutrons (UCN) stored in a magneto-gravitational trap. The trap employs various techniques to remove neutrons whose energies are too high to be trapped. It has recently been instrumented with a novel in situ detector that can be lowered into the trap to measure the neutron population as a function of height within the trap. This has allowed us to perform a series of systematic studies aimed at understanding and quantifying potential systematic effects associated with quasi-bound neutrons and phase space evolution. We have obtained multiple sets of data each having a statistical uncertainty of about 3 sec. We will discuss the results of our studies of cleaning and phase space evolution as well as results from studies of backgrounds and normalization of the initial neutron loading.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wu, Yuan; Bei, Hongbin; Wang, Yanli
Deformation behavior and local strain evolutions upon loading and unloading of a bulk metallic glass (BMG) were systematically investigated by in situ digital image correlation (DIC). Distinct fluctuations and irreversible local strains were observed before the onset of macroscopic yielding. Statistical analysis shows that these fluctuations might be related to intrinsic structural heterogeneities, and that the evolution history and characteristics of local strain fields play an important role in the subsequent initiation of shear bands. Effects of sample size, pre-strain, and loading conditions were systematically analyzed in terms of the probability distributions of the resulting local strain fields. It ismore » found that a higher degree of local shear strain heterogeneity corresponds to a more ductile stressestrain curve. Implications of these findings are discussed for the design of new materials.« less
Wu, Yuan; Bei, Hongbin; Wang, Yanli; ...
2015-05-16
Deformation behavior and local strain evolutions upon loading and unloading of a bulk metallic glass (BMG) were systematically investigated by in situ digital image correlation (DIC). Distinct fluctuations and irreversible local strains were observed before the onset of macroscopic yielding. Statistical analysis shows that these fluctuations might be related to intrinsic structural heterogeneities, and that the evolution history and characteristics of local strain fields play an important role in the subsequent initiation of shear bands. Effects of sample size, pre-strain, and loading conditions were systematically analyzed in terms of the probability distributions of the resulting local strain fields. It ismore » found that a higher degree of local shear strain heterogeneity corresponds to a more ductile stressestrain curve. Implications of these findings are discussed for the design of new materials.« less
Evidence of Twisted Flux-Tube Emergence in Active Regions
NASA Astrophysics Data System (ADS)
Poisson, M.; Mandrini, C. H.; Démoulin, P.; López Fuentes, M.
2015-03-01
Elongated magnetic polarities are observed during the emergence phase of bipolar active regions (ARs). These extended features, called magnetic tongues, are interpreted as a consequence of the azimuthal component of the magnetic flux in the toroidal flux-tubes that form ARs. We develop a new systematic and user-independent method to identify AR tongues. Our method is based on determining and analyzing the evolution of the AR main polarity inversion line (PIL). The effect of the tongues is quantified by measuring the acute angle [ τ] between the orientation of the PIL and the direction orthogonal to the AR main bipolar axis. We apply a simple model to simulate the emergence of a bipolar AR. This model lets us interpret the effect of magnetic tongues on parameters that characterize ARs ( e.g. the PIL inclination and the tilt angles, and their evolution). In this idealized kinematic emergence model, τ is a monotonically increasing function of the twist and has the same sign as the magnetic helicity. We systematically apply our procedure to a set of bipolar ARs (41 ARs) that were observed emerging in line-of-sight magnetograms over eight years. For most of the cases studied, the tongues only have a small influence on the AR tilt angle since tongues have a much lower magnetic flux than the more concentrated main polarities. From the observed evolution of τ, corrected for the temporal evolution of the tilt angle and its final value when the AR is fully emerged, we estimate the average number of turns in the subphotospherically emerging flux-rope. These values for the 41 observed ARs are below unity, except for one. This indicates that subphotospheric flux-ropes typically have a low amount of twist, i.e. highly twisted flux-tubes are rare. Our results demonstrate that the evolution of the PIL is a robust indicator of the presence of tongues and constrains the amount of twist in emerging flux-tubes.
Compartmentalized partnered replication for the directed evolution of genetic parts and circuits.
Abil, Zhanar; Ellefson, Jared W; Gollihar, Jimmy D; Watkins, Ella; Ellington, Andrew D
2017-12-01
Compartmentalized partnered replication (CPR) is an emulsion-based directed evolution method based on a robust and modular phenotype-genotype linkage. In contrast to other in vivo directed evolution approaches, CPR largely mitigates host fitness effects due to a relatively short expression time of the gene of interest. CPR is based on gene circuits in which the selection of a 'partner' function from a library leads to the production of a thermostable polymerase. After library preparation, bacteria produce partner proteins that can potentially lead to enhancement of transcription, translation, gene regulation, and other aspects of cellular metabolism that reinforce thermostable polymerase production. Individual cells are then trapped in water-in-oil emulsion droplets in the presence of primers and dNTPs, followed by the recovery of the partner genes via emulsion PCR. In this step, droplets with cells expressing partner proteins that promote polymerase production will produce higher copy numbers of the improved partner gene. The resulting partner genes can subsequently be recloned for the next round of selection. Here, we present a step-by-step guideline for the procedure by providing examples of (i) selection of T7 RNA polymerases that recognize orthogonal promoters and (ii) selection of tRNA for enhanced amber codon suppression. A single round of CPR should take ∼3-5 d, whereas a whole directed evolution can be performed in 3-10 rounds, depending on selection efficiency.
2016-01-01
Introduction Sickle cell disease causes chronic haemolytic anaemia, dactylitis, and painful acute crises. It also increases the risk of stroke, organ damage, bacterial infections, and complications of blood transfusion. In sub-Saharan Africa, up to one third of adults are carriers of the defective sickle cell gene, and 1% to 2% of babies are born with the disease. Methods and outcomes We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of pharmaceutical interventions to prevent sickle cell crisis and other acute complications in people with sickle cell disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2015 (BMJ Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). Results At this update, searching of electronic databases retrieved 369 studies. After deduplication and removal of conference abstracts, 136 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 99 studies and the further review of 37 full publications. Of the 37 full articles evaluated, three already included systematic reviews were updated, two systematic reviews, two RCTs, and one subsequent RCT were added at this update. We performed a GRADE evaluation for 12 PICO combinations. Conclusions In this systematic overview, we categorised the efficacy for five interventions based on information about the effectiveness and safety of antibiotic prophylaxis in children aged under 5 years, antibiotic prophylaxis in children aged 5 years or older, hydroxyurea, malaria chemoprophylaxis, and pneumococcal vaccines. PMID:26808098
A Stochastic Framework for Modeling the Population Dynamics of Convective Clouds
Hagos, Samson; Feng, Zhe; Plant, Robert S.; ...
2018-02-20
A stochastic prognostic framework for modeling the population dynamics of convective clouds and representing them in climate models is proposed. The framework follows the nonequilibrium statistical mechanical approach to constructing a master equation for representing the evolution of the number of convective cells of a specific size and their associated cloud-base mass flux, given a large-scale forcing. In this framework, referred to as STOchastic framework for Modeling Population dynamics of convective clouds (STOMP), the evolution of convective cell size is predicted from three key characteristics of convective cells: (i) the probability of growth, (ii) the probability of decay, and (iii)more » the cloud-base mass flux. STOMP models are constructed and evaluated against CPOL radar observations at Darwin and convection permitting model (CPM) simulations. Multiple models are constructed under various assumptions regarding these three key parameters and the realisms of these models are evaluated. It is shown that in a model where convective plumes prefer to aggregate spatially and the cloud-base mass flux is a nonlinear function of convective cell area, the mass flux manifests a recharge-discharge behavior under steady forcing. Such a model also produces observed behavior of convective cell populations and CPM simulated cloud-base mass flux variability under diurnally varying forcing. Finally, in addition to its use in developing understanding of convection processes and the controls on convective cell size distributions, this modeling framework is also designed to serve as a nonequilibrium closure formulations for spectral mass flux parameterizations.« less
A Stochastic Framework for Modeling the Population Dynamics of Convective Clouds
NASA Astrophysics Data System (ADS)
Hagos, Samson; Feng, Zhe; Plant, Robert S.; Houze, Robert A.; Xiao, Heng
2018-02-01
A stochastic prognostic framework for modeling the population dynamics of convective clouds and representing them in climate models is proposed. The framework follows the nonequilibrium statistical mechanical approach to constructing a master equation for representing the evolution of the number of convective cells of a specific size and their associated cloud-base mass flux, given a large-scale forcing. In this framework, referred to as STOchastic framework for Modeling Population dynamics of convective clouds (STOMP), the evolution of convective cell size is predicted from three key characteristics of convective cells: (i) the probability of growth, (ii) the probability of decay, and (iii) the cloud-base mass flux. STOMP models are constructed and evaluated against CPOL radar observations at Darwin and convection permitting model (CPM) simulations. Multiple models are constructed under various assumptions regarding these three key parameters and the realisms of these models are evaluated. It is shown that in a model where convective plumes prefer to aggregate spatially and the cloud-base mass flux is a nonlinear function of convective cell area, the mass flux manifests a recharge-discharge behavior under steady forcing. Such a model also produces observed behavior of convective cell populations and CPM simulated cloud-base mass flux variability under diurnally varying forcing. In addition to its use in developing understanding of convection processes and the controls on convective cell size distributions, this modeling framework is also designed to serve as a nonequilibrium closure formulations for spectral mass flux parameterizations.
A Stochastic Framework for Modeling the Population Dynamics of Convective Clouds
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hagos, Samson; Feng, Zhe; Plant, Robert S.
A stochastic prognostic framework for modeling the population dynamics of convective clouds and representing them in climate models is proposed. The framework follows the nonequilibrium statistical mechanical approach to constructing a master equation for representing the evolution of the number of convective cells of a specific size and their associated cloud-base mass flux, given a large-scale forcing. In this framework, referred to as STOchastic framework for Modeling Population dynamics of convective clouds (STOMP), the evolution of convective cell size is predicted from three key characteristics of convective cells: (i) the probability of growth, (ii) the probability of decay, and (iii)more » the cloud-base mass flux. STOMP models are constructed and evaluated against CPOL radar observations at Darwin and convection permitting model (CPM) simulations. Multiple models are constructed under various assumptions regarding these three key parameters and the realisms of these models are evaluated. It is shown that in a model where convective plumes prefer to aggregate spatially and the cloud-base mass flux is a nonlinear function of convective cell area, the mass flux manifests a recharge-discharge behavior under steady forcing. Such a model also produces observed behavior of convective cell populations and CPM simulated cloud-base mass flux variability under diurnally varying forcing. Finally, in addition to its use in developing understanding of convection processes and the controls on convective cell size distributions, this modeling framework is also designed to serve as a nonequilibrium closure formulations for spectral mass flux parameterizations.« less
Ultra-high-throughput screening method for the directed evolution of glucose oxidase.
Ostafe, Raluca; Prodanovic, Radivoje; Nazor, Jovana; Fischer, Rainer
2014-03-20
Glucose oxidase (GOx) is used in many industrial processes that could benefit from improved versions of the enzyme. Some improvements like higher activity under physiological conditions and thermal stability could be useful for GOx applications in biosensors and biofuel cells. Directed evolution is one of the currently available methods to engineer improved GOx variants. Here, we describe an ultra-high-throughput screening system for sorting the best enzyme variants generated by directed evolution that incorporates several methodological refinements: flow cytometry, in vitro compartmentalization, yeast surface display, fluorescent labeling of the expressed enzyme, delivery of glucose substrate to the reaction mixture through the oil phase, and covalent labeling of the cells with fluorescein-tyramide. The method enables quantitative screening of gene libraries to identify clones with improved activity and it also allows cells to be selected based not only on the overall activity but also on the specific activity of the enzyme. Copyright © 2014 Elsevier Ltd. All rights reserved.
Lineage Tracking for Probing Heritable Phenotypes at Single-Cell Resolution
Cottinet, Denis; Condamine, Florence; Bremond, Nicolas; Griffiths, Andrew D.; Rainey, Paul B.; de Visser, J. Arjan G. M.; Baudry, Jean; Bibette, Jérôme
2016-01-01
Determining the phenotype and genotype of single cells is central to understand microbial evolution. DNA sequencing technologies allow the detection of mutants at high resolution, but similar approaches for phenotypic analyses are still lacking. We show that a drop-based millifluidic system enables the detection of heritable phenotypic changes in evolving bacterial populations. At time intervals, cells were sampled and individually compartmentalized in 100 nL drops. Growth through 15 generations was monitored using a fluorescent protein reporter. Amplification of heritable changes–via growth–over multiple generations yields phenotypically distinct clusters reflecting variation relevant for evolution. To demonstrate the utility of this approach, we follow the evolution of Escherichia coli populations during 30 days of starvation. Phenotypic diversity was observed to rapidly increase upon starvation with the emergence of heritable phenotypes. Mutations corresponding to each phenotypic class were identified by DNA sequencing. This scalable lineage-tracking technology opens the door to large-scale phenotyping methods with special utility for microbiology and microbial population biology. PMID:27077662
Lineage Tracking for Probing Heritable Phenotypes at Single-Cell Resolution.
Cottinet, Denis; Condamine, Florence; Bremond, Nicolas; Griffiths, Andrew D; Rainey, Paul B; de Visser, J Arjan G M; Baudry, Jean; Bibette, Jérôme
2016-01-01
Determining the phenotype and genotype of single cells is central to understand microbial evolution. DNA sequencing technologies allow the detection of mutants at high resolution, but similar approaches for phenotypic analyses are still lacking. We show that a drop-based millifluidic system enables the detection of heritable phenotypic changes in evolving bacterial populations. At time intervals, cells were sampled and individually compartmentalized in 100 nL drops. Growth through 15 generations was monitored using a fluorescent protein reporter. Amplification of heritable changes-via growth-over multiple generations yields phenotypically distinct clusters reflecting variation relevant for evolution. To demonstrate the utility of this approach, we follow the evolution of Escherichia coli populations during 30 days of starvation. Phenotypic diversity was observed to rapidly increase upon starvation with the emergence of heritable phenotypes. Mutations corresponding to each phenotypic class were identified by DNA sequencing. This scalable lineage-tracking technology opens the door to large-scale phenotyping methods with special utility for microbiology and microbial population biology.
Microbial detection method based on sensing molecular hydrogen
NASA Technical Reports Server (NTRS)
Wilkins, J. R.; Stoner, G. E.; Boykin, E. H.
1974-01-01
A simple method for detecting bacteria, based on the time of hydrogen evolution, was developed and tested against various members of the Enterobacteriaceae group. The test system consisted of (1) two electrodes, platinum and a reference electrode, (2) a buffer amplifier, and (3) a strip-chart recorder. Hydrogen evolution was measured by an increase in voltage in the negative (cathodic) direction. A linear relationship was established between inoculum size and the time hydrogen was detected (lag period). Lag times ranged from 1 h for 1 million cells/ml to 7 h for 1 cell/ml. For each 10-fold decrease in inoculum, length of the lag period increased 60 to 70 min. Based on the linear relationship between inoculum and lag period, these results indicate the potential application of the hydrogen-sensing method for rapidly detecting coliforms and other gas-producing microorganisms in a variety of clinical, food, and other samples.
Torlakovic, Emina E; Cheung, Carol C; D'Arrigo, Corrado; Dietel, Manfred; Francis, Glenn D; Gilks, C Blake; Hall, Jacqueline A; Hornick, Jason L; Ibrahim, Merdol; Marchetti, Antonio; Miller, Keith; van Krieken, J Han; Nielsen, Soren; Swanson, Paul E; Vyberg, Mogens; Zhou, Xiaoge; Taylor, Clive R
2017-02-01
All laboratory tests have test performance characteristics (TPCs), whether or not they are explicitly known to the laboratorian or the pathologist. TPCs are thus also an integral characteristic of immunohistochemistry (IHC) tests and other in situ, cell-based molecular assays such as DNA or RNA in situ hybridization or aptamer-based testing. Because of their descriptive, in situ, cell-based nature, IHC tests have a limited repertoire of appropriate TPCs. Although only a few TPCs are relevant to IHC, proper selection of informative TPCs is nonetheless essential for the development of and adherence to appropriate quality assurance measures in the IHC laboratory. This paper describes the TPCs that are relevant to IHC testing and emphasizes the role of TPCs in the validation of IHC tests. This is part 2 of the 4-part series "Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine."
Coastline evolution of Portuguese low-lying sandy coast in the last 50 years: an integrated approach
NASA Astrophysics Data System (ADS)
Ponte Lira, Cristina; Nobre Silva, Ana; Taborda, Rui; Freire de Andrade, Cesar
2016-06-01
Regional/national-scale information on coastline rates of change and trends is extremely valuable, but these studies are scarce. A widely accepted standardized methodology for analysing long-term coastline change has been difficult to achieve, but it is essential to conduct an integrated and holistic approach to coastline evolution and hence support coastal management actions. Additionally, databases providing knowledge on coastline evolution are of key importance to support both coastal management experts and users.The main objective of this work is to present the first systematic, national-scale and consistent long-term coastline evolution data of Portuguese mainland low-lying sandy coasts.The methodology used quantifies coastline evolution using a unique and robust coastline indicator (the foredune toe), which is independent of short-term changes.The dataset presented comprises (1) two polyline sets, mapping the 1958 and 2010 sandy beach-dune system coastline, both optimized for working at 1 : 50 000 scale or smaller; (2) one polyline set representing long-term change rates between 1958 and 2010, each estimated at 250 m; and (3) a table with minimum, maximum and mean of evolution rates for sandy beach-dune system coastline. All science data produced here are openly accessible at https://doi.pangaea.de/10.1594/PANGAEA.859136 and can be used in other studies.Results show beach erosion as the dominant trend, with a mean change rate of -0.24 ± 0.01 m year-1 for all mainland Portuguese beach-dune systems. Although erosion is dominant, this evolution is variable in signal and magnitude in different coastal sediment cells and also within each cell. The most relevant beach erosion issues were found in the coastal stretches of Espinho-Torreira and Costa Nova-Praia de Mira, Cova da Gala-Leirosa, and Cova do Vapor-Costa da Caparica. The coastal segments Minho River-Nazaré and Costa da Caparica adjacent to the coast exhibit a history of major human interventions interfering with the coastal system, many of which originated and maintained a sediment deficit. In contrast, the coastal segments Troia-Sines and Sines-Cape S. Vicente have experienced less intervention and show stable or moderate accretion behaviour.
The B7 family of immunoregulatory receptors: A comparative and evolutionary perspective
Hansen, J.D.; Pasquier, L.D.; Lefranc, M.-P.; Lopez, V.; Benmansour, A.; Boudinot, P.
2009-01-01
In mammals, T cell activation requires specific recognition of the peptide-MHC complex by the TcR and co-stimulatory signals. Important co-stimulatory receptors expressed by T cells are the molecules of the CD28 family, that regulate T cell activation, proliferation and tolerance. These receptors recognize B7s and B7-homologous (B7H) molecules that are typically expressed by the antigen presenting cells. In teleost fish, typical T cell responses have been described and the TcR, MHC and CD28/CTLA4 genes have been characterized. In contrast, the members of the B7 gene family have only been described in mammals and birds and have yet to be addressed in lower vertebrates. To learn more about the evolution of components guiding T cell activation in vertebrates, we performed a systematic genomic survey for the B7 co-stimulatory and co-inhibitory IgSF receptors in lower vertebrates with an emphasis on teleost fish. Our search identified fish sequences that are orthologous to B7, B7-H1/B7-DC, B7-H3 and B7-H4 as defined by sequence identity, phylogeny and combinations of short or long-range syntenic relationships. However, we were unable to identify clear orthologs for B7-H2 (CD275, ICOS ligand) in bony fish, which correlates with our prior inability to find ICOS in fish. Interestingly, our results indicate that teleost fish possess a single B7.1/B7.2 (CD80/86) molecule that likely interacts with CD28/CTLA4 as the ligand-binding regions seem to be conserved in both partners. Overall, our analyses implies that gene duplication (and loss) have shaped a molecular repertoire of B7-like molecules that was recruited for the refinement of T cell activation during the evolution of the vertebrates.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mukerjee, S.; Thurston, T.R.; Jisrawi, N.M.
The authors describe synchrotron based X-ray diffraction techniques and issues related to in situ studies of intercalation processes in battery electrodes. They then demonstrate the utility of this technique, through a study of two batches of Li{sub x}Mn{sub 2}O{sub 4} cathode materials. The structural evolution of these spinel materials was monitored in situ during the initial charge of these electrodes in actual battery cells. Significant differences were observed in the two batches, particularly in the intercalation range of x = 0.45 to 0.20. The first-order structural transitions in this region indicated coexistence of two cubic phases in the batch 2more » material, whereas the batch 1 material showed suppressed two-phase coexistence. Batch 2 cells also indicated structural evolution in the low-potential region below 3.0 V in contrast to the batch 1 material. Differences in structural evolution between batches of Li{sub x}Mn{sub 2}O{sub 4} could have important ramifications in their cycle life and stability characteristics.« less
Five rules for the evolution of cooperation.
Nowak, Martin A
2006-12-08
Cooperation is needed for evolution to construct new levels of organization. Genomes, cells, multicellular organisms, social insects, and human society are all based on cooperation. Cooperation means that selfish replicators forgo some of their reproductive potential to help one another. But natural selection implies competition and therefore opposes cooperation unless a specific mechanism is at work. Here I discuss five mechanisms for the evolution of cooperation: kin selection, direct reciprocity, indirect reciprocity, network reciprocity, and group selection. For each mechanism, a simple rule is derived that specifies whether natural selection can lead to cooperation.
Five Rules for the Evolution of Cooperation
NASA Astrophysics Data System (ADS)
Nowak, Martin A.
2006-12-01
Cooperation is needed for evolution to construct new levels of organization. Genomes, cells, multicellular organisms, social insects, and human society are all based on cooperation. Cooperation means that selfish replicators forgo some of their reproductive potential to help one another. But natural selection implies competition and therefore opposes cooperation unless a specific mechanism is at work. Here I discuss five mechanisms for the evolution of cooperation: kin selection, direct reciprocity, indirect reciprocity, network reciprocity, and group selection. For each mechanism, a simple rule is derived that specifies whether natural selection can lead to cooperation.
Imperative role of dental pulp stem cells in regenerative therapies: a systematic review.
Kabir, Ramchandra; Gupta, Manish; Aggarwal, Avanti; Sharma, Deepak; Sarin, Anurag; Kola, Mohammed Zaheer
2014-01-01
Stem cells are primitive cells that can differentiate and regenerate organs in different parts of the body such as heart, bones, muscles and nervous system. This has been a field of great clinical interest with immense possibilities of using the stem cells in regeneration of human organ those are damaged due to disease, developmental defects and accident. The knowledge of stem cell technology is increasing quickly in all medical specialties and in dental field too. Stem cells of dental origin appears to hold the key to various cell-based therapies in regenerative medicine, but most avenues are in experimental stages and many procedures are undergoing standardization and validation. Long-term preservation of SHED cells or DPSC is becoming a popular consideration, similar to the banking of umbilical cord blood. Dental pulp stem cells (DPSCs) are the adult multipotent cells that reside in the cell rich zone of the dental pulp. The multipotent nature of these DPSCs may be utilized in both dental and medical applications. A systematic review of the literature was performed using various internet based search engines (PubMed, Medline Plus, Cochrane, Medknow, Ebsco, Science Direct, Hinari, WebMD, IndMed, Embase) using keywords like "dental pulp stem cells", "regeneration", "medical applications", "tissue engineering". DPSCs appears to be a promising innovation for the re-growth of tissues however, long term clinical studies need to be carried out that could establish some authentic guidelines in this perspective.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhou, C
2009-11-12
In FY09 they will (1) complete the implementation, verification, calibration, and sensitivity and scalability analysis of the in-cell virus replication model; (2) complete the design of the cell culture (cell-to-cell infection) model; (3) continue the research, design, and development of their bioinformatics tools: the Web-based structure-alignment-based sequence variability tool and the functional annotation of the genome database; (4) collaborate with the University of California at San Francisco on areas of common interest; and (5) submit journal articles that describe the in-cell model with simulations and the bioinformatics approaches to evaluation of genome variability and fitness.
Gaillard, Jean-Michel; Lemaître, Jean-François
2017-12-01
Williams' evolutionary theory of senescence based on antagonistic pleiotropy has become a landmark in evolutionary biology, and more recently in biogerontology and evolutionary medicine. In his original article, Williams launched a set of nine "testable deductions" from his theory. Although some of these predictions have been repeatedly discussed, most have been overlooked and no systematic evaluation of the whole set of Williams' original predictions has been performed. For the sixtieth anniversary of the publication of the Williams' article, we provide an updated evaluation of all these predictions. We present the pros and cons of each prediction based on recent accumulation of both theoretical and empirical studies performed in the laboratory and in the wild. From our viewpoint, six predictions are mostly supported by our current knowledge at least under some conditions (although Williams' theory cannot thoroughly explain why for some of them). Three predictions, all involving the timing of senescence, are not supported. Our critical review of Williams' predictions highlights the importance of William's contribution and clearly demonstrates that, 60 years after its publication, his article does not show any sign of senescence. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.
TRIZ: A Bridge Between Applied and Industrial Physics
NASA Astrophysics Data System (ADS)
Savransky, Semyon
1997-03-01
TRIZ provides a methodology for creative engineering design. TRIZ was founded by Genrich S. Altshuller in Russia, whose with co-workers analyses about 1,500,000 worldwide patents. The major TRIZ principles are [1,2]: 1. All engineering systems have uniform evolution. Many other systems (economic, educational, etc.) have the same evolution trends. 2. Any inventive problem represents a conflict between new requirements and old system. TRIZ comprises various systematically techniques to find an quasi-ideal answer to the inventive problem through solve the conflict based on the knowledge of a system evolution. Usually the hidden root of technical problem is physical contradictions that is possible to resolve using the lists of effects. TRIZ experts use a knowledge base of applied physics to provide solutions of industrial problems . Many companies around the world cite a phenomenal increase in the producti-vity and quality of solutions to tough engineering problems through the use of TRIZ. [1]. G. S. Altshuller, B.L. Zlotin, A.V. Zusman and V.I. Filatov, The new ideas search: From intuition to technology. (in Russian) Kishinev, 1989, 381p. [2]. S.D. Savransky, and C. Stephan, TRIZ: Methodology of Inventive Problem Solving. The Indust-rial Physicist (December 1996).
Acevedo-Rocha, Carlos G; Agudo, Ruben; Reetz, Manfred T
2014-12-10
Directed evolution of stereoselective enzymes provides a means to generate useful biocatalysts for asymmetric transformations in organic chemistry and biotechnology. Almost all of the numerous examples reported in the literature utilize high-throughput screening systems based on suitable analytical techniques. Since the screening step is the bottleneck of the overall procedure, researchers have considered the use of genetic selection systems as an alternative to screening. In principle, selection would be the most elegant and efficient approach because it is based on growth advantage of host cells harboring stereoselective mutants, but devising such selection systems is very challenging. They must be designed so that the host organism profits from the presence of an enantioselective variant. Progress in this intriguing research area is summarized in this review, which also includes some examples of display systems designed for enantioselectivity as assayed by fluorescence-activated cell sorting (FACS). Although the combination of display systems and FACS is a powerful approach, we also envision innovative ideas combining metabolic engineering and genetic selection systems with protein directed evolution for the development of highly selective and efficient biocatalysts. Copyright © 2014 Elsevier B.V. All rights reserved.
Dissecting cancer evolution at the macro-heterogeneity and micro-heterogeneity scale.
Barber, Louise J; Davies, Matthew N; Gerlinger, Marco
2015-02-01
Intratumour heterogeneity complicates biomarker discovery and treatment personalization, and pervasive cancer evolution is a key mechanism leading to therapy failure and patient death. Thus, understanding subclonal heterogeneity architectures and cancer evolution processes is critical for the development of effective therapeutic approaches which can control or thwart cancer evolutionary plasticity. Current insights into heterogeneity are mainly limited to the macroheterogeneity level, established by cancer subclones that have undergone significant clonal expansion. Novel single cell sequencing and blood-based subclonal tracking technologies are enabling detailed insights into microheterogeneity and the dynamics of clonal evolution. We assess how this starts to delineate the rules governing cancer evolution and novel angles for more effective therapeutic intervention. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
Advanced continuous cultivation methods for systems microbiology.
Adamberg, Kaarel; Valgepea, Kaspar; Vilu, Raivo
2015-09-01
Increasing the throughput of systems biology-based experimental characterization of in silico-designed strains has great potential for accelerating the development of cell factories. For this, analysis of metabolism in the steady state is essential as only this enables the unequivocal definition of the physiological state of cells, which is needed for the complete description and in silico reconstruction of their phenotypes. In this review, we show that for a systems microbiology approach, high-resolution characterization of metabolism in the steady state--growth space analysis (GSA)--can be achieved by using advanced continuous cultivation methods termed changestats. In changestats, an environmental parameter is continuously changed at a constant rate within one experiment whilst maintaining cells in the physiological steady state similar to chemostats. This increases the resolution and throughput of GSA compared with chemostats, and, moreover, enables following of the dynamics of metabolism and detection of metabolic switch-points and optimal growth conditions. We also describe the concept, challenge and necessary criteria of the systematic analysis of steady-state metabolism. Finally, we propose that such systematic characterization of the steady-state growth space of cells using changestats has value not only for fundamental studies of metabolism, but also for systems biology-based metabolic engineering of cell factories.
Metaresearch for Evaluating Reproducibility in Ecology and Evolution.
Fidler, Fiona; Chee, Yung En; Wintle, Bonnie C; Burgman, Mark A; McCarthy, Michael A; Gordon, Ascelin
2017-03-01
Recent replication projects in other disciplines have uncovered disturbingly low levels of reproducibility, suggesting that those research literatures may contain unverifiable claims. The conditions contributing to irreproducibility in other disciplines are also present in ecology. These include a large discrepancy between the proportion of "positive" or "significant" results and the average statistical power of empirical research, incomplete reporting of sampling stopping rules and results, journal policies that discourage replication studies, and a prevailing publish-or-perish research culture that encourages questionable research practices. We argue that these conditions constitute sufficient reason to systematically evaluate the reproducibility of the evidence base in ecology and evolution. In some cases, the direct replication of ecological research is difficult because of strong temporal and spatial dependencies, so here, we propose metaresearch projects that will provide proxy measures of reproducibility.
Toward a systematic design theory for silicon solar cells using optimization techniques
NASA Technical Reports Server (NTRS)
Misiakos, K.; Lindholm, F. A.
1986-01-01
This work is a first detailed attempt to systematize the design of silicon solar cells. Design principles follow from three theorems. Although the results hold only under low injection conditions in base and emitter regions, they hold for arbitrary doping profiles and include the effects of drift fields, high/low junctions and heavy doping concentrations of donor or acceptor atoms. Several optimal designs are derived from the theorems, one of which involves a three-dimensional morphology in the emitter region. The theorems are derived from a nonlinear differential equation of the Riccati form, the dependent variable of which is a normalized recombination particle current.
Kipf, Elena; Koch, Julia; Geiger, Bettina; Erben, Johannes; Richter, Katrin; Gescher, Johannes; Zengerle, Roland; Kerzenmacher, Sven
2013-10-01
We present a systematic screening of carbon-based anode materials for microbial fuel cells with Shewanella oneidensis MR-1. Under anoxic conditions nanoporous activated carbon cloth is a superior anode material in terms of current density normalized to the projected anode area and anode volume (24.0±0.3 μA cm(-2) and 482±7 μA cm(-3) at -0.2 vs. SCE, respectively). The good performance can be attributed to the high specific surface area of the material, which is available for mediated electron transfer through self-secreted flavins. Under aerated conditions no influence of the specific surface area is observed, which we attribute to a shift from primary indirect electron transfer by mediators to direct electron transfer via adherent cells. Furthermore, we show that an aerated initial growth phase enhances the current density under subsequent anoxic conditions fivefold when compared to a similar experiment that was conducted under permanently anoxic conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.
Unrean, Pornkamol; Khajeeram, Sutamat; Laoteng, Kobkul
2016-03-01
An integrative simultaneous saccharification and fermentation (SSF) modeling is a useful guiding tool for rapid process optimization to meet the techno-economic requirement of industrial-scale lignocellulosic ethanol production. In this work, we have developed the SSF model composing of a metabolic network of a Saccharomyces cerevisiae cell associated with fermentation kinetics and enzyme hydrolysis model to quantitatively capture dynamic responses of yeast cell growth and fermentation during SSF. By using model-based design of feeding profiles for substrate and yeast cell in the fed-batch SSF process, an efficient ethanol production with high titer of up to 65 g/L and high yield of 85 % of theoretical yield was accomplished. The ethanol titer and productivity was increased by 47 and 41 %, correspondingly, in optimized fed-batch SSF as compared to batch process. The developed integrative SSF model is, therefore, considered as a promising approach for systematic design of economical and sustainable SSF bioprocessing of lignocellulose.
Schuberth, Christian; Won, Hong-Hee; Blattmann, Peter; Joggerst-Thomalla, Brigitte; Theiss, Susanne; Asselta, Rosanna; Duga, Stefano; Merlini, Pier Angelica; Ardissino, Diego; Lander, Eric S.; Gabriel, Stacey; Rader, Daniel J.; Peloso, Gina M.; Kathiresan, Sekar; Runz, Heiko
2015-01-01
A fundamental challenge to contemporary genetics is to distinguish rare missense alleles that disrupt protein functions from the majority of alleles neutral on protein activities. High-throughput experimental tools to securely discriminate between disruptive and non-disruptive missense alleles are currently missing. Here we establish a scalable cell-based strategy to profile the biological effects and likely disease relevance of rare missense variants in vitro. We apply this strategy to systematically characterize missense alleles in the low-density lipoprotein receptor (LDLR) gene identified through exome sequencing of 3,235 individuals and exome-chip profiling of 39,186 individuals. Our strategy reliably identifies disruptive missense alleles, and disruptive-allele carriers have higher plasma LDL-cholesterol (LDL-C). Importantly, considering experimental data refined the risk of rare LDLR allele carriers from 4.5- to 25.3-fold for high LDL-C, and from 2.1- to 20-fold for early-onset myocardial infarction. Our study generates proof-of-concept that systematic functional variant profiling may empower rare variant-association studies by orders of magnitude. PMID:25647241
Keck Deep Fields. II. The Ultraviolet Galaxy Luminosity Function at z ~ 4, 3, and 2
NASA Astrophysics Data System (ADS)
Sawicki, Marcin; Thompson, David
2006-05-01
We use very deep UnGRI multifield imaging obtained at the Keck telescope to study the evolution of the rest-frame 1700 Å galaxy luminosity function as the universe doubles its age from z~4 to ~2. We use exactly the same filters and color-color selection as those used by the Steidel team but probe significantly fainter limits, well below L*. The depth of our imaging allows us to constrain the faint end of the luminosity function, reaching M1700~-18.5 at z~3 (equivalent to ~1 Msolar yr-1), accounting for both N1/2 uncertainty in the number of galaxies and cosmic variance. We carefully examine many potential sources of systematic bias in our LF measurements before drawing the following conclusions. We find that the luminosity function of Lyman break galaxies evolves with time and that this evolution is differential with luminosity. The result is best constrained between the epochs at z~4 and ~3, where we find that the number density of sub-L* galaxies increases with time by at least a factor of 2.3 (11 σ statistical confidence); while the faint end of the LF evolves, the bright end appears to remain virtually unchanged, indicating that there may be differential, luminosity-dependent evolution (98.5% statistical probability). Potential systematic biases restrict our ability to draw strong conclusions about continued evolution of the luminosity function to lower redshifts, z~2.2 and ~1.7, but, nevertheless, it appears certain that the number density of z~2.2 galaxies at all luminosities we studied, -22>M1700>-18, is at least as high as that of their counterparts at z~3. While it is not yet clear what mechanism underlies the observed evolution, the fact that this evolution is differential with luminosity opens up new avenues of improving our understanding of how galaxies form and evolve at high redshift. Based on data obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and NASA and was made possible by the generous financial support of the W. M. Keck Foundation.
Networking Omic Data to Envisage Systems Biological Regulation.
Kalapanulak, Saowalak; Saithong, Treenut; Thammarongtham, Chinae
To understand how biological processes work, it is necessary to explore the systematic regulation governing the behaviour of the processes. Not only driving the normal behavior of organisms, the systematic regulation evidently underlies the temporal responses to surrounding environments (dynamics) and long-term phenotypic adaptation (evolution). The systematic regulation is, in effect, formulated from the regulatory components which collaboratively work together as a network. In the drive to decipher such a code of lives, a spectrum of technologies has continuously been developed in the post-genomic era. With current advances, high-throughput sequencing technologies are tremendously powerful for facilitating genomics and systems biology studies in the attempt to understand system regulation inside the cells. The ability to explore relevant regulatory components which infer transcriptional and signaling regulation, driving core cellular processes, is thus enhanced. This chapter reviews high-throughput sequencing technologies, including second and third generation sequencing technologies, which support the investigation of genomics and transcriptomics data. Utilization of this high-throughput data to form the virtual network of systems regulation is explained, particularly transcriptional regulatory networks. Analysis of the resulting regulatory networks could lead to an understanding of cellular systems regulation at the mechanistic and dynamics levels. The great contribution of the biological networking approach to envisage systems regulation is finally demonstrated by a broad range of examples.
Multiphysics of bone remodeling: A 2D mesoscale activation simulation.
Spingarn, C; Wagner, D; Rémond, Y; George, D
2017-01-01
In this work, we present an evolutive trabecular model for bone remodeling based on a boundary detection algorithm accounting for both biology and applied mechanical forces, known to be an important factor in bone evolution. A finite element (FE) numerical model using the Abaqus/Standard® software was used with a UMAT subroutine to solve the governing coupled mechanical-biological non-linear differential equations of the bone evolution model. The simulations present cell activation on a simplified trabeculae configuration organization with trabecular thickness of 200µm. For this activation process, the results confirm that the trabeculae are mainly oriented in the active direction of the principal mechanical stresses and according to the principal applied mechanical load directions. The trabeculae surface activation is clearly identified and can provide understanding of the different bone cell activations in more complex geometries and load conditions.
Imperative Role of Dental Pulp Stem Cells in Regenerative Therapies: A Systematic Review
Kabir, Ramchandra; Gupta, Manish; Aggarwal, Avanti; Sharma, Deepak; Sarin, Anurag; Kola, Mohammed Zaheer
2014-01-01
Stem cells are primitive cells that can differentiate and regenerate organs in different parts of the body such as heart, bones, muscles and nervous system. This has been a field of great clinical interest with immense possibilities of using the stem cells in regeneration of human organ those are damaged due to disease, developmental defects and accident. The knowledge of stem cell technology is increasing quickly in all medical specialties and in dental field too. Stem cells of dental origin appears to hold the key to various cell-based therapies in regenerative medicine, but most avenues are in experimental stages and many procedures are undergoing standardization and validation. Long-term preservation of SHED cells or DPSC is becoming a popular consideration, similar to the banking of umbilical cord blood. Dental pulp stem cells (DPSCs) are the adult multipotent cells that reside in the cell rich zone of the dental pulp. The multipotent nature of these DPSCs may be utilized in both dental and medical applications. A systematic review of the literature was performed using various internet based search engines (PubMed, Medline Plus, Cochrane, Medknow, Ebsco, Science Direct, Hinari, WebMD, IndMed, Embase) using keywords like “dental pulp stem cells”, “regeneration”, “medical applications”, “tissue engineering”. DPSCs appears to be a promising innovation for the re-growth of tissues however, long term clinical studies need to be carried out that could establish some authentic guidelines in this perspective. PMID:24665194
Cytodifferentiation of hair cells during the development of a basal chordate.
Gasparini, Fabio; Caicci, Federico; Rigon, Francesca; Zaniolo, Giovanna; Burighel, Paolo; Manni, Lucia
2013-10-01
Tunicates are unique animals for studying the origin and evolution of vertebrates because they are considered vertebrates' closest living relatives and share the vertebrate body plan and many specific features. Both possess neural placodes, transient thickenings of the cranial ectoderm that give rise to various types of sensory cells, including axonless secondary mechanoreceptors. In vertebrates, these are represented by the hair cells of the inner ear and the lateral line, which have an apical apparatus typically bearing cilia and stereovilli. In tunicates, they are found in the coronal organ, which is a mechanoreceptor located at the base of the oral siphon along the border of the velum and tentacles and is formed of cells bearing a row of cilia and short microvilli. The coronal organ represents the best candidate homolog for the vertebrate lateral line. To further understand the evolution of secondary sensory cells, we analysed the development and cytodifferentiation of coronal cells in the tunicate ascidian Ciona intestinalis for the first time. Here, coronal sensory cells can be identified as early as larval metamorphosis, before tentacles form, as cells with short cilia and microvilli. Sensory cells gradually differentiate, acquiring hair cell features with microvilli containing actin and myosin VIIa; in the meantime, the associated supporting cells develop. The coronal organ grows throughout the animal's lifespan, accompanying the growth of the tentacle crown. Anti-phospho Histone H3 immunostaining indicates that both hair cells and supporting cells can proliferate. This finding contributes to the understanding of the evolution of secondary sensory cells, suggesting that both ancestral cell types were able to proliferate and that this property was progressively restricted to supporting cells in vertebrates and definitively lost in mammals. Copyright © 2013 Elsevier B.V. All rights reserved.
Hyde, Christopher; Peters, Jaime; Bond, Mary; Rogers, Gabriel; Hoyle, Martin; Anderson, Rob; Jeffreys, Mike; Davis, Sarah; Thokala, Praveen; Moxham, Tiffany
2013-01-01
in 2007 the National Institute of Health and Clinical Excellence (NICE) restricted the use of acetylcholinesterase inhibitors and memantine. we conducted a health technology assessment (HTA) of the effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine and memantine for the treatment of AD to re-consider and up-date the evidence base used to inform the 2007 NICE decision. The systematic review of effectiveness targeted randomised controlled trials. A comprehensive search, including MEDLINE, Embase and the Cochrane Library, was conducted from January 2004 to March 2010. All key review steps were done by two reviewers. Random effects meta-analysis was conducted. The cost-effectiveness was assessed using a cohort-based model with three health states: pre-institutionalised, institutionalised and dead. The perspective was NHS and Personal Social Services and the cost year 2009. confidence about the size and statistical significance of the estimates of effect of galantamine, rivastigmine and memantine improved on function and global impact in particular. Cost-effectiveness also changed. For donepezil, galantamine and rivastigmine, the incremental cost per quality-adjusted life year (QALY) in 2004 was above £50,000; in 2010 the same drugs 'dominated' best supportive care (improved clinical outcome at reduced cost). This was primarily because of changes in the modelled costs of introducing the drugs. For memantine, the cost-effectiveness also improved from a range of £37-53,000 per QALY gained to a base-case of £32,000. there has been a change in the evidence base between 2004 and 2010 consistent with the change in NICE guidance. Further evolution in cost-effectiveness estimates is possible particularly if there are changes in drug prices.
Damage evolution analysis of coal samples under cyclic loading based on single-link cluster method
NASA Astrophysics Data System (ADS)
Zhang, Zhibo; Wang, Enyuan; Li, Nan; Li, Xuelong; Wang, Xiaoran; Li, Zhonghui
2018-05-01
In this paper, the acoustic emission (AE) response of coal samples under cyclic loading is measured. The results show that there is good positive relation between AE parameters and stress. The AE signal of coal samples under cyclic loading exhibits an obvious Kaiser Effect. The single-link cluster (SLC) method is applied to analyze the spatial evolution characteristics of AE events and the damage evolution process of coal samples. It is found that a subset scale of the SLC structure becomes smaller and smaller when the number of cyclic loading increases, and there is a negative linear relationship between the subset scale and the degree of damage. The spatial correlation length ξ of an SLC structure is calculated. The results show that ξ fluctuates around a certain value from the second cyclic loading process to the fifth cyclic loading process, but spatial correlation length ξ clearly increases in the sixth loading process. Based on the criterion of microcrack density, the coal sample failure process is the transformation from small-scale damage to large-scale damage, which is the reason for changes in the spatial correlation length. Through a systematic analysis, the SLC method is an effective method to research the damage evolution process of coal samples under cyclic loading, and will provide important reference values for studying coal bursts.
Zúñiga-Reinoso, Álvaro; Méndez, Marco A
2018-04-24
The origin of cryptic species has traditionally been associated with events of recent speciation, genetic constraints, selection of an adaptive character, sexual selection and/or convergent evolution. Species of the genus Callyntra inhabit coastal terraces, mountain slopes, and peaks; their elytral designs are associated with each of these habitats. However, cryptic species have been described within each of these habitats; the taxonomy of this group has been problematic, thus establishing the phylogenetic relationships in this group is fundamental to clarify the systematics and evolutionary patterns of Callyntra. We reconstructed the phylogeny of this group using two mitochondrial genes (COI, 16S) and one nuclear gene (Mp20). We also performed species delimitation using PTP based methods (PTP, mlPTP, bPTP) and GMYC, and evaluated the evolution of the elytral design related to habitat preference. The results showed a tree with five clades, that together with the different methods of species delimitation recovered the described species and suggested at least five new species. The elytral design and habitat preference showed phylogenetic signals. We propose a new classification based on monophyletic groups recovered by phylogenetic analyses. We also suggest that parallel evolution in different habitats and later stasis in the elytral design would be the cause of the origin of cryptic species in this group from central Chile. Copyright © 2018 Elsevier Inc. All rights reserved.
Noble metal-free bifunctional oxygen evolution and oxygen reduction acidic media electro-catalysts
DOE Office of Scientific and Technical Information (OSTI.GOV)
Patel, Prasad Prakash; Datta, Moni Kanchan; Velikokhatnyi, Oleg I.
We report that identification of low cost, highly active, durable completely noble metal-free electro-catalyst for oxygen reduction reaction (ORR) in proton exchange membrane (PEM) fuel cells, oxygen evolution reaction (OER) in PEM based water electrolysis and metal air batteries remains one of the major unfulfilled scientific and technological challenges of PEM based acid mediated electro-catalysts. In contrast, several non-noble metals based electro-catalysts have been identified for alkaline and neutral medium water electrolysis and fuel cells. Furthermore, we report for the very first time, F doped Cu 1.5Mn 1.5O 4, identified by exploiting theoretical first principles calculations for ORR and OERmore » in PEM based systems. The identified novel noble metal-free electro-catalyst showed similar onset potential (1.43 V for OER and 1 V for ORR vs RHE) to that of IrO 2 and Pt/C, respectively. The system also displayed excellent electrochemical activity comparable to IrO 2 for OER and Pt/C for ORR, respectively, along with remarkable long term stability for 6000 cycles in acidic media validating theory, while also displaying superior methanol tolerance and yielding recommended power densities in full cell configurations.« less
Noble metal-free bifunctional oxygen evolution and oxygen reduction acidic media electro-catalysts
Patel, Prasad Prakash; Datta, Moni Kanchan; Velikokhatnyi, Oleg I.; ...
2016-07-06
We report that identification of low cost, highly active, durable completely noble metal-free electro-catalyst for oxygen reduction reaction (ORR) in proton exchange membrane (PEM) fuel cells, oxygen evolution reaction (OER) in PEM based water electrolysis and metal air batteries remains one of the major unfulfilled scientific and technological challenges of PEM based acid mediated electro-catalysts. In contrast, several non-noble metals based electro-catalysts have been identified for alkaline and neutral medium water electrolysis and fuel cells. Furthermore, we report for the very first time, F doped Cu 1.5Mn 1.5O 4, identified by exploiting theoretical first principles calculations for ORR and OERmore » in PEM based systems. The identified novel noble metal-free electro-catalyst showed similar onset potential (1.43 V for OER and 1 V for ORR vs RHE) to that of IrO 2 and Pt/C, respectively. The system also displayed excellent electrochemical activity comparable to IrO 2 for OER and Pt/C for ORR, respectively, along with remarkable long term stability for 6000 cycles in acidic media validating theory, while also displaying superior methanol tolerance and yielding recommended power densities in full cell configurations.« less
Noble metal-free bifunctional oxygen evolution and oxygen reduction acidic media electro-catalysts
Patel, Prasad Prakash; Datta, Moni Kanchan; Velikokhatnyi, Oleg I.; Kuruba, Ramalinga; Damodaran, Krishnan; Jampani, Prashanth; Gattu, Bharat; Shanthi, Pavithra Murugavel; Damle, Sameer S.; Kumta, Prashant N.
2016-01-01
Identification of low cost, highly active, durable completely noble metal-free electro-catalyst for oxygen reduction reaction (ORR) in proton exchange membrane (PEM) fuel cells, oxygen evolution reaction (OER) in PEM based water electrolysis and metal air batteries remains one of the major unfulfilled scientific and technological challenges of PEM based acid mediated electro-catalysts. In contrast, several non-noble metals based electro-catalysts have been identified for alkaline and neutral medium water electrolysis and fuel cells. Herein we report for the very first time, F doped Cu1.5Mn1.5O4, identified by exploiting theoretical first principles calculations for ORR and OER in PEM based systems. The identified novel noble metal-free electro-catalyst showed similar onset potential (1.43 V for OER and 1 V for ORR vs RHE) to that of IrO2 and Pt/C, respectively. The system also displayed excellent electrochemical activity comparable to IrO2 for OER and Pt/C for ORR, respectively, along with remarkable long term stability for 6000 cycles in acidic media validating theory, while also displaying superior methanol tolerance and yielding recommended power densities in full cell configurations. PMID:27380719
Noble metal-free bifunctional oxygen evolution and oxygen reduction acidic media electro-catalysts
NASA Astrophysics Data System (ADS)
Patel, Prasad Prakash; Datta, Moni Kanchan; Velikokhatnyi, Oleg I.; Kuruba, Ramalinga; Damodaran, Krishnan; Jampani, Prashanth; Gattu, Bharat; Shanthi, Pavithra Murugavel; Damle, Sameer S.; Kumta, Prashant N.
2016-07-01
Identification of low cost, highly active, durable completely noble metal-free electro-catalyst for oxygen reduction reaction (ORR) in proton exchange membrane (PEM) fuel cells, oxygen evolution reaction (OER) in PEM based water electrolysis and metal air batteries remains one of the major unfulfilled scientific and technological challenges of PEM based acid mediated electro-catalysts. In contrast, several non-noble metals based electro-catalysts have been identified for alkaline and neutral medium water electrolysis and fuel cells. Herein we report for the very first time, F doped Cu1.5Mn1.5O4, identified by exploiting theoretical first principles calculations for ORR and OER in PEM based systems. The identified novel noble metal-free electro-catalyst showed similar onset potential (1.43 V for OER and 1 V for ORR vs RHE) to that of IrO2 and Pt/C, respectively. The system also displayed excellent electrochemical activity comparable to IrO2 for OER and Pt/C for ORR, respectively, along with remarkable long term stability for 6000 cycles in acidic media validating theory, while also displaying superior methanol tolerance and yielding recommended power densities in full cell configurations.
Noble metal-free bifunctional oxygen evolution and oxygen reduction acidic media electro-catalysts.
Patel, Prasad Prakash; Datta, Moni Kanchan; Velikokhatnyi, Oleg I; Kuruba, Ramalinga; Damodaran, Krishnan; Jampani, Prashanth; Gattu, Bharat; Shanthi, Pavithra Murugavel; Damle, Sameer S; Kumta, Prashant N
2016-07-06
Identification of low cost, highly active, durable completely noble metal-free electro-catalyst for oxygen reduction reaction (ORR) in proton exchange membrane (PEM) fuel cells, oxygen evolution reaction (OER) in PEM based water electrolysis and metal air batteries remains one of the major unfulfilled scientific and technological challenges of PEM based acid mediated electro-catalysts. In contrast, several non-noble metals based electro-catalysts have been identified for alkaline and neutral medium water electrolysis and fuel cells. Herein we report for the very first time, F doped Cu1.5Mn1.5O4, identified by exploiting theoretical first principles calculations for ORR and OER in PEM based systems. The identified novel noble metal-free electro-catalyst showed similar onset potential (1.43 V for OER and 1 V for ORR vs RHE) to that of IrO2 and Pt/C, respectively. The system also displayed excellent electrochemical activity comparable to IrO2 for OER and Pt/C for ORR, respectively, along with remarkable long term stability for 6000 cycles in acidic media validating theory, while also displaying superior methanol tolerance and yielding recommended power densities in full cell configurations.
Erren, T C; Erren, M
2004-04-01
When David Horrobin suggested that phospholipid and fatty acid metabolism played a major role in human evolution, his 'fat utilization hypothesis' unified intriguing work from paleoanthropology, evolutionary biology, genetic and nervous system research in a novel and coherent lipid-related context. Interestingly, unlike most other evolutionary concepts, the hypothesis allows specific predictions which can be empirically tested in the near future. This paper summarizes some of Horrobin's intriguing propositions and suggests as to how approaches of comparative genomics published in Cell, Nature, Science and elsewhere since 1997 may be used to examine his evolutionary hypothesis. Indeed, systematic investigations of the genomic clock in the species' mitochondrial DNA, the Y and autosomal chromosomes as evidence of evolutionary relationships and distinctions can help to scrutinize associated predictions for their validity, namely that key mutations which differentiate us from Neanderthals and from great apes are in the genes coding for proteins which regulate fat metabolism, and particularly the phospholipid metabolism of the synapses of the brain. It is concluded that beyond clues to humans' relationships with living primates and to the Neanderthals' cognitive performance and their disappearance, the suggested molecular clock analyses may provide crucial insights into the biochemical evolution-and means of possible manipulation-of our brain.
Modelling of Damage Evolution in Braided Composites: Recent Developments
NASA Astrophysics Data System (ADS)
Wang, Chen; Roy, Anish; Silberschmidt, Vadim V.; Chen, Zhong
2017-12-01
Composites reinforced with woven or braided textiles exhibit high structural stability and excellent damage tolerance thanks to yarn interlacing. With their high stiffness-to-weight and strength-to-weight ratios, braided composites are attractive for aerospace and automotive components as well as sports protective equipment. In these potential applications, components are typically subjected to multi-directional static, impact and fatigue loadings. To enhance material analysis and design for such applications, understanding mechanical behaviour of braided composites and development of predictive capabilities becomes crucial. Significant progress has been made in recent years in development of new modelling techniques allowing elucidation of static and dynamic responses of braided composites. However, because of their unique interlacing geometric structure and complicated failure modes, prediction of damage initiation and its evolution in components is still a challenge. Therefore, a comprehensive literature analysis is presented in this work focused on a review of the state-of-the-art progressive damage analysis of braided composites with finite-element simulations. Recently models employed in the studies on mechanical behaviour, impact response and fatigue analyses of braided composites are presented systematically. This review highlights the importance, advantages and limitations of as-applied failure criteria and damage evolution laws for yarns and composite unit cells. In addition, this work provides a good reference for future research on FE simulations of braided composites.
Somogyi, Endre; Glazier, James A.
2017-01-01
Biological cells are the prototypical example of active matter. Cells sense and respond to mechanical, chemical and electrical environmental stimuli with a range of behaviors, including dynamic changes in morphology and mechanical properties, chemical uptake and secretion, cell differentiation, proliferation, death, and migration. Modeling and simulation of such dynamic phenomena poses a number of computational challenges. A modeling language describing cellular dynamics must naturally represent complex intra and extra-cellular spatial structures and coupled mechanical, chemical and electrical processes. Domain experts will find a modeling language most useful when it is based on concepts, terms and principles native to the problem domain. A compiler must then be able to generate an executable model from this physically motivated description. Finally, an executable model must efficiently calculate the time evolution of such dynamic and inhomogeneous phenomena. We present a spatial hybrid systems modeling language, compiler and mesh-free Lagrangian based simulation engine which will enable domain experts to define models using natural, biologically motivated constructs and to simulate time evolution of coupled cellular, mechanical and chemical processes acting on a time varying number of cells and their environment. PMID:29303160
Somogyi, Endre; Glazier, James A
2017-04-01
Biological cells are the prototypical example of active matter. Cells sense and respond to mechanical, chemical and electrical environmental stimuli with a range of behaviors, including dynamic changes in morphology and mechanical properties, chemical uptake and secretion, cell differentiation, proliferation, death, and migration. Modeling and simulation of such dynamic phenomena poses a number of computational challenges. A modeling language describing cellular dynamics must naturally represent complex intra and extra-cellular spatial structures and coupled mechanical, chemical and electrical processes. Domain experts will find a modeling language most useful when it is based on concepts, terms and principles native to the problem domain. A compiler must then be able to generate an executable model from this physically motivated description. Finally, an executable model must efficiently calculate the time evolution of such dynamic and inhomogeneous phenomena. We present a spatial hybrid systems modeling language, compiler and mesh-free Lagrangian based simulation engine which will enable domain experts to define models using natural, biologically motivated constructs and to simulate time evolution of coupled cellular, mechanical and chemical processes acting on a time varying number of cells and their environment.
Systematic study on the discharge product of Pt-based lithium oxygen batteries
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wu, Feng; Xing, Yi; Bi, Xuanxuan
Lithium oxygen batteries have attracted much attention due to the high theoretical energy density. However, they suffer a large overpotential during oxygen evolution process and thus catalysts play a vital role in the reaction. Here, we systematically explored the influence of Pt-based nanoparticle catalysts on the discharge product Li 2O 2. Because of the superior electrical conductivity and the strong binding with oxygen, Pt-based nanoparticles serve as active sites which are favorable for the growth of toroidal Li 2O 2. We also found that the content and composition of Pt-based nanoparticle catalysts exert a significant influence on the electrochemical performancemore » of lithium oxygen batteries. The discharge products are composed of crystalline Li 2O 2 and oxygen-rich LiO 2 characterized by high-energy X-ray diffraction and Raman. Atomic force microscopy further provides detailed information of the particle size and surface roughness. The loading of Pt catalysts determines the phase and size of Li 2O 2 on the discharged electrode surface. This study will be beneficial for the optimization of Pt-based catalysts used in non-aqueous lithium oxygen batteries.« less
Systematic study on the discharge product of Pt-based lithium oxygen batteries
NASA Astrophysics Data System (ADS)
Wu, Feng; Xing, Yi; Bi, Xuanxuan; Yuan, Yifei; Wang, Hsien-Hau; Shahbazian-Yassar, Reza; Li, Li; Chen, Renjie; Lu, Jun; Amine, Khalil
2016-11-01
Lithium oxygen batteries have attracted much attention due to the high theoretical energy density. However, they suffer a large overpotential during oxygen evolution process and thus catalysts play a vital role in the reaction. Here, we systematically explored the influence of Pt-based nanoparticle catalysts on the discharge product Li2O2. Because of the superior electrical conductivity and the strong binding with oxygen, Pt-based nanoparticles serve as active sites which are favorable for the growth of toroidal Li2O2. We also found that the content and composition of Pt-based nanoparticle catalysts exert a significant influence on the electrochemical performance of lithium oxygen batteries. The discharge products are composed of crystalline Li2O2 and oxygen-rich LiO2 characterized by high-energy X-ray diffraction and Raman. Atomic force microscopy further provides detailed information of the particle size and surface roughness. The loading of Pt catalysts determines the phase and size of Li2O2 on the discharged electrode surface. This study will be beneficial for the optimization of Pt-based catalysts used in non-aqueous lithium oxygen batteries.
Molecular recognition of live methicillin-resistant staphylococcus aureus cells using DNA aptamers
Turek, Diane; Van Simaeys, Dimitri; Johnson, Judith; Ocsoy, Ismail; Tan, Weihong
2014-01-01
AIM To generate DNA-aptamers binding to Methicillin-resistant Staphylococcus aureus (MRSA). METHODS The Cell-Systematic Evolution of Ligands by Exponential Enrichment (SELEX) technology was used to run the selection against MRSA bacteria and develop target-specific aptamers. MRSA bacteria were targeted while Enterococcus faecalis bacteria were used for counter selection during that process. Binding assays to determine the right aptamer candidates as well as binding assays on clinical samples were performed through flow cytometry and analyzed using the FlowJo software. The characterization of the aptamers was done by determination of their Kd values and determined by analysis of flow data at different aptamer concentration using SigmaPlot. Finally, the recognition of the complex Gold-nanoparticle-aptamer to the bacteria cells was observed using transmission electron microscopy (TEM). RESULTS During the cell-SELEX selection process, 17 rounds were necessary to generate enrichment of the pool. While the selection was run using fixed cells, it was shown that the binding of the pools with live cells was giving similar results. After sequencing and analysis of the two last pools, four sequences were identified to be aptamer candidates. The characterization of those aptamers showed that based on their Kd values, DTMRSA4 presented the best binding with a Kd value of 94.61 ± 18.82 nmol/L. A total of ten clinical samples of MRSA , S. aureus and Enterococcus faecalis were obtained to test those aptamers and determine their binding on a panel of samples. DTMRSA1 and DTMRSA3 showed the best results regarding their specificity to MRSA , DTMRSA1 being the most specific of all. Finally, those aptamers were coupled with gold-nanoparticle and their binding to MRSA cells was visualized through TEM showing that adduction of nanoparticles on the aptamers did not change their binding property. CONCLUSION A total of four aptamers that bind to MRSA were obtained with Kd values ranking from 94 to 200 nmol/L. PMID:25436184
Molecular recognition of live methicillin-resistant staphylococcus aureus cells using DNA aptamers.
Turek, Diane; Van Simaeys, Dimitri; Johnson, Judith; Ocsoy, Ismail; Tan, Weihong
2013-01-01
To generate DNA-aptamers binding to Methicillin-resistant Staphylococcus aureus (MRSA) . The Cell-Systematic Evolution of Ligands by Exponential Enrichment (SELEX) technology was used to run the selection against MRSA bacteria and develop target-specific aptamers. MRSA bacteria were targeted while Enterococcus faecalis bacteria were used for counter selection during that process. Binding assays to determine the right aptamer candidates as well as binding assays on clinical samples were performed through flow cytometry and analyzed using the FlowJo software. The characterization of the aptamers was done by determination of their K d values and determined by analysis of flow data at different aptamer concentration using SigmaPlot. Finally, the recognition of the complex Gold-nanoparticle-aptamer to the bacteria cells was observed using transmission electron microscopy (TEM). During the cell-SELEX selection process, 17 rounds were necessary to generate enrichment of the pool. While the selection was run using fixed cells, it was shown that the binding of the pools with live cells was giving similar results. After sequencing and analysis of the two last pools, four sequences were identified to be aptamer candidates. The characterization of those aptamers showed that based on their K d values, DTMRSA4 presented the best binding with a K d value of 94.61 ± 18.82 nmol/L. A total of ten clinical samples of MRSA , S. aureus and Enterococcus faecalis were obtained to test those aptamers and determine their binding on a panel of samples. DTMRSA1 and DTMRSA3 showed the best results regarding their specificity to MRSA , DTMRSA1 being the most specific of all. Finally, those aptamers were coupled with gold-nanoparticle and their binding to MRSA cells was visualized through TEM showing that adduction of nanoparticles on the aptamers did not change their binding property. A total of four aptamers that bind to MRSA were obtained with K d values ranking from 94 to 200 nmol/L.
Composition and development of oral bacterial communities.
Palmer, Robert J
2014-02-01
The oral bacterial microbiome encompasses approximately 700 commonly occurring phylotypes, approximately half of which can be present at any time in any individual. These bacteria are largely indigenous to the oral cavity; this limited habitat range suggests that interactions between the various phylotypes, and between the phylotypes and their environment, are crucial for their existence. Molecular cataloging has confirmed many basic observations on the composition of the oral microbiome that were formulated well before ribosomal RNA-based systematics, but the power and the scope of molecular taxonomy have resulted in the discovery of new phylotypes and, more importantly, have made possible a level of bacterial community analysis that was unachievable with classical methods. Bacterial community structure varies with location within the mouth, and changes in community structure are related to disease initiation and disease progression. Factors that influence the formation and the evolution of communities include selective adherence to epithelial or tooth surfaces, specific cell-to-cell binding as a driver of early community composition, and interorganismal interaction leading to alteration of the local environment, which represents the first step on the road to oral disease. A comprehensive understanding of how these factors interact to drive changes in the composition of the oral microbial community can lead to new strategies for the inhibition of periodontal diseases and dental caries. Published 2013. This article is a US Government work and is in the public domain in the USA.
Bioattractors: dynamical systems theory and the evolution of regulatory processes.
Jaeger, Johannes; Monk, Nick
2014-06-01
In this paper, we illustrate how dynamical systems theory can provide a unifying conceptual framework for evolution of biological regulatory systems. Our argument is that the genotype-phenotype map can be characterized by the phase portrait of the underlying regulatory process. The features of this portrait--such as attractors with associated basins and their bifurcations--define the regulatory and evolutionary potential of a system. We show how the geometric analysis of phase space connects Waddington's epigenetic landscape to recent computational approaches for the study of robustness and evolvability in network evolution. We discuss how the geometry of phase space determines the probability of possible phenotypic transitions. Finally, we demonstrate how the active, self-organizing role of the environment in phenotypic evolution can be understood in terms of dynamical systems concepts. This approach yields mechanistic explanations that go beyond insights based on the simulation of evolving regulatory networks alone. Its predictions can now be tested by studying specific, experimentally tractable regulatory systems using the tools of modern systems biology. A systematic exploration of such systems will enable us to understand better the nature and origin of the phenotypic variability, which provides the substrate for evolution by natural selection. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.
Paul, Angela; Avci-Adali, Meltem; Ziemer, Gerhard; Wendel, Hans P
2009-09-01
Using whole living cells as a target for SELEX (systematic evolution of ligands by exponential enrichment) experiments represents a promising method to generate cell receptor-specific aptamers. These aptamers have a huge potential in diagnostics, therapeutics, imaging, regenerative medicine, and target validation. During the SELEX for selecting DNA aptamers, one important step is the separation of 2 DNA strands to yield one of the 2 strands as single-stranded DNA aptamer. This is being done routinely by biotin labeling of the complementary DNA strand to the desired aptamer and then separating the DNA strand by using streptavidin-coated magnetic beads. After immobilization of the double-stranded DNA on these magnetic beads and alkaline denaturation, the non-biotinylated strand is being eluted and the biotinylated strand is retarded. Using Western blot analysis, we demonstrated the detachment of covalent-bonded streptavidin from the bead surface after alkaline treatment. The eluates were also contaminated with undesired biotinylated strands. Furthermore, a streptavidin-induced aggregation of target cells was demonstrated by flow cytometry and microscopic methods. Cell-specific enrichment of aptamers was not possible due to clustering and patching effects triggered by streptavidin. Therefore, the use of streptavidin-coated magnetic beads for DNA strand separation should be examined thoroughly, especially for cell-SELEX applications.
Cummins, Carla A; McInerney, James O
2011-12-01
Current phylogenetic methods attempt to account for evolutionary rate variation across characters in a matrix. This is generally achieved by the use of sophisticated evolutionary models, combined with dense sampling of large numbers of characters. However, systematic biases and superimposed substitutions make this task very difficult. Model adequacy can sometimes be achieved at the cost of adding large numbers of free parameters, with each parameter being optimized according to some criterion, resulting in increased computation times and large variances in the model estimates. In this study, we develop a simple approach that estimates the relative evolutionary rate of each homologous character. The method that we describe uses the similarity between characters as a proxy for evolutionary rate. In this article, we work on the premise that if the character-state distribution of a homologous character is similar to many other characters, then this character is likely to be relatively slowly evolving. If the character-state distribution of a homologous character is not similar to many or any of the rest of the characters in a data set, then it is likely to be the result of rapid evolution. We show that in some test cases, at least, the premise can hold and the inferences are robust. Importantly, the method does not use a "starting tree" to make the inference and therefore is tree independent. We demonstrate that this approach can work as well as a maximum likelihood (ML) approach, though the ML method needs to have a known phylogeny, or at least a very good estimate of that phylogeny. We then demonstrate some uses for this method of analysis, including the improvement in phylogeny reconstruction for both deep-level and recent relationships and overcoming systematic biases such as base composition bias. Furthermore, we compare this approach to two well-established methods for reweighting or removing characters. These other methods are tree-based and we show that they can be systematically biased. We feel this method can be useful for phylogeny reconstruction, understanding evolutionary rate variation, and for understanding selection variation on different characters.
Systematic study of inorganic functionalization of ZnO nanorods by Sol-Gel method
NASA Astrophysics Data System (ADS)
Gamarra, J. K.; Solano, C.; Piñeres, I.; Gómez, H.; Mass, J.; Montenegro, D. N.
2017-01-01
A systematic study of the inorganic surface functionalization of ZnO nanostructures by sol-gel method is shown. We have emphasized on the evolution of morphology properties of samples as a function of functionalization parameters. In addition, the effects on thermal stability and some optical properties of samples are discussed.
Measurement of Systematic effects in the UCN τ neutron lifetime experiment
NASA Astrophysics Data System (ADS)
Callahan, Nathan; UCNtau Collaboration
2017-09-01
The UCN τ experiment at the Los Alamos Neutron Science Center (LANSCe) measures the neutron β decay lifetime (τn) by trapping Ultracold Neutrons (UCN) in a magneto-gravitational trap. UCN are confined from below by magnetic fields and above by gravity. UCN are loaded into the trap, held for times on the order of τn, and counted. Several systematic effects can potentially shift the measured τn including heating and other losses of UCN during storage, insufficient removal of UCN with energies above the traping potential, and phase space evolution of UCN during storage which can cause changes in detection efficiency. The UCN τ collaboration has put limits on these systematic effects via measurements in the 2016-2017 run cycle at LANSCE. For the first two effects, a limit is placed by searching for high-energy UCN at the end of storage. A limit is placed on the effects of phase space evolution by comparing arrival time distributions for UCN under different conditions. Data from the 2016-2017 run cycle and systematic limits derived from it will be discussed.
ERIC Educational Resources Information Center
Iiskala, Tuike; Volet, Simone; Lehtinen, Erno; Vauras, Marja
2015-01-01
The significance of socially shared metacognitive regulation (SSMR) in collaborative learning is gaining momentum. To date, however, there is still a paucity of research of how SSMR is manifested in asynchronous computer-supported collaborative learning (CSCL), and hardly any systematic investigation of SSMR's functions and evolution across…
Huang, Sha; Hou, Han Wei; Kanias, Tamir; Sertorio, Jonas Tadeu; Chen, Huichao; Sinchar, Derek; Gladwin, Mark T; Han, Jongyoon
2015-01-21
In this study, the effects of prolonged storage on several biophysical properties of red blood cells (RBCs) were investigated. Single cell deformability was used as an important criterion in determining subgroups of RBCs evolved during storage lesion. A deformability-based microfluidic cell sorting technology was applied, which demonstrates the ability to enrich and separate the less deformable subpopulations of stored blood. These less deformable RBC subpopulations were then associated with other important markers such as osmotic fragility indicating cell integrity as well as microparticle content. This work demonstrates a systematic methodology to both monitor and improve banked blood quality, thereby reducing risks related to blood transfusion.
Satellite Power Systems (SPS) Concept Definition Study. Volume 3: SPS Concept Evolution
NASA Technical Reports Server (NTRS)
Hanley, G.
1978-01-01
A solar photovoltaic satellite based upon the utilization of a GaAlAs solar cell is defined. Topics covered include silicon-based photovoltaics, solar thermal power conversion, microwave energy transmission, power distribution, structures, attitude control and stationkeeping, thermal, and information management and control.
Deniaud-Bouët, Estelle; Kervarec, Nelly; Michel, Gurvan; Tonon, Thierry; Kloareg, Bernard; Hervé, Cécile
2014-10-01
Brown algae are photosynthetic multicellular marine organisms evolutionarily distant from land plants, with a distinctive cell wall. They feature carbohydrates shared with plants (cellulose), animals (fucose-containing sulfated polysaccharides, FCSPs) or bacteria (alginates). How these components are organized into a three-dimensional extracellular matrix (ECM) still remains unclear. Recent molecular analysis of the corresponding biosynthetic routes points toward a complex evolutionary history that shaped the ECM structure in brown algae. Exhaustive sequential extractions and composition analyses of cell wall material from various brown algae of the order Fucales were performed. Dedicated enzymatic degradations were used to release and identify cell wall partners. This approach was complemented by systematic chromatographic analysis to study polymer interlinks further. An additional structural assessment of the sulfated fucan extracted from Himanthalia elongata was made. The data indicate that FCSPs are tightly associated with proteins and cellulose within the walls. Alginates are associated with most phenolic compounds. The sulfated fucans from H. elongata were shown to have a regular α-(1→3) backbone structure, while an alternating α-(1→3), (1→4) structure has been described in some brown algae from the order Fucales. The data provide a global snapshot of the cell wall architecture in brown algae, and contribute to the understanding of the structure-function relationships of the main cell wall components. Enzymatic cross-linking of alginates by phenols may regulate the strengthening of the wall, and sulfated polysaccharides may play a key role in the adaptation to osmotic stress. The emergence and evolution of ECM components is further discussed in relation to the evolution of multicellularity in brown algae. © The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Assessing Technical Competence in Surgical Trainees: A Systematic Review.
Szasz, Peter; Louridas, Marisa; Harris, Kenneth A; Aggarwal, Rajesh; Grantcharov, Teodor P
2015-06-01
To systematically examine the literature describing the methods by which technical competence is assessed in surgical trainees. The last decade has witnessed an evolution away from time-based surgical education. In response, governing bodies worldwide have implemented competency-based education paradigms. The definition of competence, however, remains elusive, and the impact of these education initiatives in terms of assessment methods remains unclear. A systematic review examining the methods by which technical competence is assessed was conducted by searching MEDLINE, EMBASE, PsychINFO, and the Cochrane database of systematic reviews. Abstracts of retrieved studies were reviewed and those meeting inclusion criteria were selected for full review. Data were retrieved in a systematic manner, the validity and reliability of the assessment methods was evaluated, and quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation classification. Of the 6814 studies identified, 85 studies involving 2369 surgical residents were included in this review. The methods used to assess technical competence were categorized into 5 groups; Likert scales (37), benchmarks (31), binary outcomes (11), novel tools (4), and surrogate outcomes (2). Their validity and reliability were mostly previously established. The overall Grading of Recommendations Assessment, Development and Evaluation for randomized controlled trials was high and low for the observational studies. The definition of technical competence continues to be debated within the medical literature. The methods used to evaluate technical competence predominantly include instruments that were originally created to assess technical skill. Very few studies identify standard setting approaches that differentiate competent versus noncompetent performers; subsequently, this has been identified as an area with great research potential.
Breinholt, Jesse W.; Porter, Megan L.; Crandall, Keith A.
2012-01-01
Background The genus Cambarus is one of three most species rich crayfish genera in the Northern Hemisphere. The genus has its center of diversity in the Southern Appalachians of the United States and has been divided into 12 subgenera. Using Cambarus we test the correspondence of subgeneric designations based on morphology used in traditional crayfish taxonomy to the underlying evolutionary history for these crayfish. We further test for significant correlation and explanatory power of geographic distance, taxonomic model, and a habitat model to estimated phylogenetic distance with multiple variable regression. Methodology/Principal Findings We use three mitochondrial and one nuclear gene regions to estimate the phylogenetic relationships for species within the genus Cambarus and test evolutionary hypotheses of relationships and associated morphological and biogeographical hypotheses. Our resulting phylogeny indicates that the genus Cambarus is polyphyletic, however we fail to reject the monophyly of Cambarus with a topology test. The majority of the Cambarus subgenera are rejected as monophyletic, suggesting the morphological characters used to define those taxa are subject to convergent evolution. While we found incongruence between taxonomy and estimated phylogenetic relationships, a multiple model regression analysis indicates that taxonomy had more explanatory power of genetic relationships than either habitat or geographic distance. Conclusions We find convergent evolution has impacted the morphological features used to delimit Cambarus subgenera. Studies of the crayfish genus Orconectes have shown gonopod morphology used to delimit subgenera is also affected by convergent evolution. This suggests that morphological diagnoses based on traditional crayfish taxonomy might be confounded by convergent evolution across the cambarids and has little utility in diagnosing relationships or defining natural groups. We further suggest that convergent morphological evolution appears to be a common occurrence in invertebrates suggesting the need for careful phylogenetically based interpretations of morphological evolution in invertebrate systematics. PMID:23049950
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhou, Nanjia; Dudnik, Alexander S.; Li, Ting I. N. G.
2015-12-31
ABSTRACT: The influence of the number-average molecular weight (Mn) on the blend film morphology and photovoltaic performance of all-polymer solar cells (APSCs) fabricated with the donor polymer poly[5-(2-hexyldodecyl)-1,3-thieno[3,4- c]pyrrole-4,6-dione-alt-5,5-(2,5-bis(3-dodecylthiophen-2-yl)- thiophene)] (PTPD3T) and acceptor polymer poly{[N,N'- bis(2-octyldodecyl)naphthalene-1,4,5,8-bis(dicarboximide)- 2,6-diyl]-alt-5,5'-(2,2'-bithiophene)} (P(NDI2OD-T2); N2200) is systematically investigated. The M n effect analysis of both PTPD3T and N2200 is enabled by implementing a polymerization strategy which produces conjugated polymers with tunable M ns. Experimental and coarse-grain modeling results reveal that systematic M n variation greatly influences both intrachain and interchain interactions and ultimately the degree of phase separation and morphology evolution. Specifically, increasing M n formore » both polymers shrinks blend film domain sizes and enhances donor-acceptor polymer-polymer interfacial areas, affording increased short-circuit current densities (J sc). However, the greater disorder and intermixed feature proliferation accompanying increasing M n promotes charge carrier recombination, reducing cell fill factors (FF). The optimized photoactive layers exhibit well-balanced exciton dissociation and charge transport characteristics, ultimately providing solar cells with a 2-fold PCE enhancement versus devices with nonoptimal M ns. Overall, it is shown that proper and precise tuning of both donor and acceptor polymer M ns is critical for optimizing APSC performance. In contrast to reports where maximum power conversion efficiencies (PCEs) are achieved for the highest M ns, the present two-dimensional M n optimization matrix strategy locates a PCE “sweet spot” at intermediate Mns of both donor and acceptor polymers. This study provides synthetic methodologies to predictably access conjugated polymers with desired M n and highlights the importance of optimizing M n for both polymer components to realize the full potential of APSC performance.« less
Bashor, Caleb J; Horwitz, Andrew A; Peisajovich, Sergio G; Lim, Wendell A
2010-01-01
The living cell is an incredibly complex entity, and the goal of predictively and quantitatively understanding its function is one of the next great challenges in biology. Much of what we know about the cell concerns its constituent parts, but to a great extent we have yet to decode how these parts are organized to yield complex physiological function. Classically, we have learned about the organization of cellular networks by disrupting them through genetic or chemical means. The emerging discipline of synthetic biology offers an additional, powerful approach to study systems. By rearranging the parts that comprise existing networks, we can gain valuable insight into the hierarchical logic of the networks and identify the modular building blocks that evolution uses to generate innovative function. In addition, by building minimal toy networks, one can systematically explore the relationship between network structure and function. Here, we outline recent work that uses synthetic biology approaches to investigate the organization and function of cellular networks, and describe a vision for a synthetic biology toolkit that could be used to interrogate the design principles of diverse systems.
Li, Wenkai; Feng, Xinru; Yan, Xing; Liu, Keyi; Deng, Le
2016-06-01
Most therapeutical nucleic acid aptamers tend to inhibit protein-protein interactions and thereby function as antagonists. Attachment of the influenza virus surface glycoprotein hemagglutinin (HA) to sialic acid-containing host cell receptors (glycan) facilitates the initial stage of viral infection. Inhibition of the attachment may result in an antiviral effect on the proliferation of the influenza virus. To develop therapeutically interesting agents, we selected two single-stranded DNA (ssDNA) aptamers specific to the HA protein of H1N1 influenza virus (A/Puerto Rico/8/1934) through a procedure of systematic evolution of ligands by exponential enrichment. As it showed a higher binding affinity for HA protein (Kd = 78 ± 1 nM), aptamer 1 was tested for its ability to interfere with HA-glycan interactions using chicken red blood cell hemagglutination and microneutralization assays, which demonstrated that it significantly suppressed the viral infection in host cells. These results indicate that the isolated ssDNA aptamer may be developed as an antiviral agent against influenza through appropriate therapeutic formulation.
Li, Haoyi; Chen, Shuangming; Zhang, Ying; Zhang, Qinghua; Jia, Xiaofan; Zhang, Qi; Gu, Lin; Sun, Xiaoming; Song, Li; Wang, Xun
2018-06-22
Great attention has been focused on the design of electrocatalysts to enable electrochemical water splitting-a technology that allows energy derived from renewable resources to be stored in readily accessible and non-polluting chemical fuels. Herein we report a bifunctional nanotube-array electrode for water splitting in alkaline electrolyte. The electrode requires the overpotentials of 58 mV and 184 mV for hydrogen and oxygen evolution reactions respectively, meanwhile maintaining remarkable long-term durability. The prominent performance is due to the systematic optimization of chemical composition and geometric structure principally-that is, abundant electrocatalytic active sites, excellent conductivity of metallic 1T' MoS 2 , synergistic effects among iron, cobalt, nickel ions, and the superaerophobicity of electrode surface for fast mass transfer. The electrode is also demonstrated to function as anode and cathode, simultaneously, delivering 10 mA cm -2 at a cell voltage of 1.429 V. Our results demonstrate substantial improvement in the design of high-efficiency electrodes for water electrolysis.
NASA Astrophysics Data System (ADS)
Zhang, Sheng; Hong, Siyu
2018-07-01
In this paper, a generalized Ablowitz-Kaup-Newell-Segur (AKNS) hierarchy in inhomogeneities of media described by variable coefficients is investigated, which includes some important nonlinear evolution equations as special cases, for example, the celebrated Korteweg-de Vries equation modeling waves on shallow water surfaces. To be specific, the known AKNS spectral problem and its time evolution equation are first generalized by embedding a finite number of differentiable and time-dependent functions. Starting from the generalized AKNS spectral problem and its generalized time evolution equation, a generalized AKNS hierarchy with variable coefficients is then derived. Furthermore, based on a systematic analysis on the time dependence of related scattering data of the generalized AKNS spectral problem, exact solutions of the generalized AKNS hierarchy are formulated through the inverse scattering transform method. In the case of reflectionless potentials, the obtained exact solutions are reduced to n-soliton solutions. It is graphically shown that the dynamical evolutions of such soliton solutions are influenced by not only the time-dependent coefficients but also the related scattering data in the process of propagations.
"The Two Brothers": Reconciling Perceptual-Cognitive and Statistical Models of Musical Evolution.
Jan, Steven
2018-01-01
While the "units, events and dynamics" of memetic evolution have been abstractly theorized (Lynch, 1998), they have not been applied systematically to real corpora in music. Some researchers, convinced of the validity of cultural evolution in more than the metaphorical sense adopted by much musicology, but perhaps skeptical of some or all of the claims of memetics, have attempted statistically based corpus-analysis techniques of music drawn from molecular biology, and these have offered strong evidence in favor of system-level change over time (Savage, 2017). This article argues that such statistical approaches, while illuminating, ignore the psychological realities of music-information grouping, the transmission of such groups with varying degrees of fidelity, their selection according to relative perceptual-cognitive salience, and the power of this Darwinian process to drive the systemic changes (such as the development over time of systems of tonal organization in music) that statistical methodologies measure. It asserts that a synthesis between such statistical approaches to the study of music-cultural change and the theory of memetics as applied to music (Jan, 2007), in particular the latter's perceptual-cognitive elements, would harness the strengths of each approach and deepen understanding of cultural evolution in music.
“The Two Brothers”: Reconciling Perceptual-Cognitive and Statistical Models of Musical Evolution
Jan, Steven
2018-01-01
While the “units, events and dynamics” of memetic evolution have been abstractly theorized (Lynch, 1998), they have not been applied systematically to real corpora in music. Some researchers, convinced of the validity of cultural evolution in more than the metaphorical sense adopted by much musicology, but perhaps skeptical of some or all of the claims of memetics, have attempted statistically based corpus-analysis techniques of music drawn from molecular biology, and these have offered strong evidence in favor of system-level change over time (Savage, 2017). This article argues that such statistical approaches, while illuminating, ignore the psychological realities of music-information grouping, the transmission of such groups with varying degrees of fidelity, their selection according to relative perceptual-cognitive salience, and the power of this Darwinian process to drive the systemic changes (such as the development over time of systems of tonal organization in music) that statistical methodologies measure. It asserts that a synthesis between such statistical approaches to the study of music-cultural change and the theory of memetics as applied to music (Jan, 2007), in particular the latter's perceptual-cognitive elements, would harness the strengths of each approach and deepen understanding of cultural evolution in music. PMID:29670551
High affinity ligands from in vitro selection: Complex targets
Morris, Kevin N.; Jensen, Kirk B.; Julin, Carol M.; Weil, Michael; Gold, Larry
1998-01-01
Human red blood cell membranes were used as a model system to determine if the systematic evolution of ligands by exponential enrichment (SELEX) methodology, an in vitro protocol for isolating high-affinity oligonucleotides that bind specifically to virtually any single protein, could be used with a complex mixture of potential targets. Ligands to multiple targets were generated simultaneously during the selection process, and the binding affinities of these ligands for their targets are comparable to those found in similar experiments against pure targets. A secondary selection scheme, deconvolution-SELEX, facilitates rapid isolation of the ligands to targets of special interest within the mixture. SELEX provides high-affinity compounds for multiple targets in a mixture and might allow a means for dissecting complex biological systems. PMID:9501188
Evolution of histone 2A for chromatin compaction in eukaryotes
Macadangdang, Benjamin R; Oberai, Amit; Spektor, Tanya; Campos, Oscar A; Sheng, Fang; Carey, Michael F; Vogelauer, Maria; Kurdistani, Siavash K
2014-01-01
During eukaryotic evolution, genome size has increased disproportionately to nuclear volume, necessitating greater degrees of chromatin compaction in higher eukaryotes, which have evolved several mechanisms for genome compaction. However, it is unknown whether histones themselves have evolved to regulate chromatin compaction. Analysis of histone sequences from 160 eukaryotes revealed that the H2A N-terminus has systematically acquired arginines as genomes expanded. Insertion of arginines into their evolutionarily conserved position in H2A of a small-genome organism increased linear compaction by as much as 40%, while their absence markedly diminished compaction in cells with large genomes. This effect was recapitulated in vitro with nucleosomal arrays using unmodified histones, indicating that the H2A N-terminus directly modulates the chromatin fiber likely through intra- and inter-nucleosomal arginine–DNA contacts to enable tighter nucleosomal packing. Our findings reveal a novel evolutionary mechanism for regulation of chromatin compaction and may explain the frequent mutations of the H2A N-terminus in cancer. DOI: http://dx.doi.org/10.7554/eLife.02792.001 PMID:24939988
A kinetic theory for age-structured stochastic birth-death processes
NASA Astrophysics Data System (ADS)
Chou, Tom; Greenman, Chris
Classical age-structured mass-action models such as the McKendrick-von Foerster equation have been extensively studied but they are structurally unable to describe stochastic fluctuations or population-size-dependent birth and death rates. Conversely, current theories that include size-dependent population dynamics (e.g., carrying capacity) cannot be easily extended to take into account age-dependent birth and death rates. In this paper, we present a systematic derivation of a new fully stochastic kinetic theory for interacting age-structured populations. By defining multiparticle probability density functions, we derive a hierarchy of kinetic equations for the stochastic evolution of an aging population undergoing birth and death. We show that the fully stochastic age-dependent birth-death process precludes factorization of the corresponding probability densities, which then must be solved by using a BBGKY-like hierarchy. Our results generalize both deterministic models and existing master equation approaches by providing an intuitive and efficient way to simultaneously model age- and population-dependent stochastic dynamics applicable to the study of demography, stem cell dynamics, and disease evolution. NSF.
Five rules for the evolution of cooperation
Nowak, Martin A.
2011-01-01
Cooperation is needed for evolution to construct new levels of organization. The emergence of genomes, cells, multi-cellular organisms, social insects and human society are all based on cooperation. Cooperation means that selfish replicators forgo some of their reproductive potential to help one another. But natural selection implies competition and therefore opposes cooperation unless a specific mechanism is at work. Here I discuss five mechanisms for the evolution of cooperation: kin selection, direct reciprocity, indirect reciprocity, network reciprocity and group selection. For each mechanism, a simple rule is derived which specifies whether natural selection can lead to cooperation. PMID:17158317
Selection of peptidoglycan-specific aptamers for bacterial cells identification.
Ferreira, Iêda Mendes; de Souza Lacerda, Camila Maria; de Faria, Lígia Santana; Corrêa, Cristiane Rodrigues; de Andrade, Antero Silva Ribeiro
2014-12-01
Peptidoglycan is a highly complex and essential macromolecule of bacterial outer cell wall; it is a heteropolymer made up of linear glycan strands cross-linked by peptides. Peptidoglycan has a particular composition which makes it a possible target for specific bacterial recognition. Aptamers are single-stranded DNA or RNA oligonucleotides that bind to target molecules with high affinity and specificity. Aptamers can be labeled with different radioisotopes and possess several properties that make them suitable for molecular imaging. The purpose of this study was to obtain aptamers for use as radiopharmaceutical in bacterial infection diagnosis. Two aptamers (Antibac1 and Antibac2) against peptidoglycan were selected through the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) methodology. The dissociation constant (Kd) for Antibac1 was 0.415 + 0.047 μM and for Antibac2 was 1.261 + 0.280 μM. These aptamers labeled with (32)P showed high affinity for Staphylococcus aureus cells. The binding to S. aureus and Escherichia coli in vitro were significantly higher than for Candida albicans and human fibroblasts, demonstrating their specificity for bacterial cells. These results point Antibac1 and Antibac2 as promising tools for bacterial infections identification.
Jia, Xiaolong; Tang, Tianhong; Cheng, Dan; Zhang, Cuihua; Zhang, Ran; Cai, Qing; Yang, Xiaoping
2015-12-01
Bioactive glass (BG)-containing carbon nanofibers (CNFs) are promising orthopaedic biomaterials. Herein, CNF composites were produced from electrospinning of polyacrylonitrile (PAN)/BG sol-gel precursor solution, followed by carbonization. Choosing 58S-type BG (mol%: 58.0% SiO2-26.3% CaO-15.7% P2O5) as the model, micro-structural evolution of CNF/BG composites was systematically evaluated in relating to aging times of BG precursor solution. With aging time prolonging, BG precursors underwent morphological changes from small sol clusters with loosely and randomly branched structure to highly crosslinked Si-network structure, showing continuous increase in solution viscosity. BG precursor solution with low viscosity could mix well with PAN solution, resulting in CNF composite with homogeneously distributed BG component. Whereas, BG precursor gel with densely crosslinked Si-network structure led to uneven distribution of BG component along final CNFs due to its significant phase separation from PAN component. Meanwhile, BG nanoparticles in CNFs demonstrated micro-structural evolution that they transited from weak to strong crystal state along with longer aging time. Biomineralization in simulated body fluid and in vitro osteoblasts proliferation were then applied to determine the bioactivity of CNF/BG composites. CNF/BG composites prepared from shorter aging time could induce both faster apatite deposition and cell proliferation rate. It was suggested weakly crystallized BG nanoparticles along CNFs dissolved fast and was able to provide numerous nucleation sites for apatite deposition, which also favored the proliferation of osteoblasts cells. Aging time could thus be a useful tool to regulate the biological features of CNF/BG composites. Copyright © 2015 Elsevier B.V. All rights reserved.
Specific immunotherapy in renal cancer: a systematic review.
Hirbod-Mobarakeh, Armin; Gordan, Hesam Addin; Zahiri, Zahra; Mirshahvalad, Mohammad; Hosseinverdi, Sima; Rini, Brian I; Rezaei, Nima
2017-02-01
Renal cell cancer (RCC) is the tenth most common malignancy in adults. In recent years, several approaches of active and passive immunotherapy have been studied extensively in clinical trials of patients with RCC. The aim of this systematic review was to assess the clinical efficacy of various approaches of specific immunotherapy in patients with RCC. We searched Medline, Scopus, CENTRAL, TRIP, DART, OpenGrey and ProQuest without any language filter through to 9 October 2015. One author reviewed search results for irrelevant and duplicate studies and two other authors independently extracted data from the studies. We collated study findings and calculated a weighted treatment effect across studies using Review Manager (version 5.3. Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration). We identified 14 controlled studies with 4013 RCC patients after excluding irrelevant and duplicate studies from 11,319 references retrieved from a literature search. Overall, five autologous tumor cell vaccines, one peptide-based vaccine, one virus-based vaccine and one dendritic cell (DC)-based vaccine were studied in nine controlled studies of active specific immunotherapies. A total of three passive immunotherapies including autologous cytokine-induced killer (CIK) cells, auto lymphocyte therapy (ALT) and autologous lymphokine-activated killer (LAK) cells were studied in four controlled studies. The clinical efficacy of tumor lysate-pulsed DCs, with CIK cells was studied in one controlled trial concurrently. The overall quality of studies was fair. Meta-analysis of seven studies showed that patients undergoing specific immunotherapy had significantly higher overall survival (OS) than those in the control group [hazard ratio (HR) = 0.72; 95% confidence interval (CI) = 0.58-0.89, p = 0.003]. In addition, a meta-analysis of four studies showed that there was a significant difference in progression-free survival (PFS) between patients undergoing specific immunotherapy and patients in control groups (HR = 0.86; 95% CI = 0.73-1, p = 0.05). Results of this systematic review suggest that some specific immunotherapies such as Reniale, ACHN-IL-2, Newcastle disease virus (NDV) virus-infected autologous tumor cells, ALT and CIK treatment could be beneficiary for the treatment of patients with RCC.
Yang, Nan; Chen, Jinqiu; Zhang, Hui; Dai, Zhiming; Yao, Huan; Ma, Xiaorong; Bai, Ju; Zhang, Yilin; Zhang, Wanggang
2017-12-01
The first-line formulation of antithymocyte globulin (ATG) remains unknown. We aimed to systematically review evidence to compare the efficacy and safety profiles of different ATGs. We did a systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort controlled studies comparing horse and rabbit ATG in immunosuppressive therapy of treatment-naïve aplastic anemia. We searched The Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov , and conference proceedings of American Society of Hematology and European Society for Blood and Marrow Transplantation annual meetings. The outcomes were 3-, 6-, and 12-month response; early mortality; relapse; and evolution. We pooled hazard ratios for relapse and odds ratios (ORs) for other outcomes using fixed-effect or random-effect models based on the heterogeneity. This study was registered with PROSPERO, number CRD42016036945. We included 1636 participants from three RCTs and 11 cohort controlled studies. Allocation to horse ATG increased 6-month response events by 86% compared with rabbit ATG. The benefit of horse ATG was mainly driven by increase in studies with non-Asian (OR 95% CI = 2.39 (1.54-3.69), p < 0.0001) and good partial response criterion (OR 95% CI = 2.73 (1.53-4.89), p = 0.0007). The early mortality and evolution were similar between groups. Compared with rabbit ATG, horse ATG had superior remission by 6 months and equivalent safety profiles in patients with treatment-naïve AA. Evidence for further responses beyond 6 to 12 months was limited.
Effect of promoter architecture on the cell-to-cell variability in gene expression.
Sanchez, Alvaro; Garcia, Hernan G; Jones, Daniel; Phillips, Rob; Kondev, Jané
2011-03-01
According to recent experimental evidence, promoter architecture, defined by the number, strength and regulatory role of the operators that control transcription, plays a major role in determining the level of cell-to-cell variability in gene expression. These quantitative experiments call for a corresponding modeling effort that addresses the question of how changes in promoter architecture affect variability in gene expression in a systematic rather than case-by-case fashion. In this article we make such a systematic investigation, based on a microscopic model of gene regulation that incorporates stochastic effects. In particular, we show how operator strength and operator multiplicity affect this variability. We examine different modes of transcription factor binding to complex promoters (cooperative, independent, simultaneous) and how each of these affects the level of variability in transcriptional output from cell-to-cell. We propose that direct comparison between in vivo single-cell experiments and theoretical predictions for the moments of the probability distribution of mRNA number per cell can be used to test kinetic models of gene regulation. The emphasis of the discussion is on prokaryotic gene regulation, but our analysis can be extended to eukaryotic cells as well.
Effect of Promoter Architecture on the Cell-to-Cell Variability in Gene Expression
Sanchez, Alvaro; Garcia, Hernan G.; Jones, Daniel; Phillips, Rob; Kondev, Jané
2011-01-01
According to recent experimental evidence, promoter architecture, defined by the number, strength and regulatory role of the operators that control transcription, plays a major role in determining the level of cell-to-cell variability in gene expression. These quantitative experiments call for a corresponding modeling effort that addresses the question of how changes in promoter architecture affect variability in gene expression in a systematic rather than case-by-case fashion. In this article we make such a systematic investigation, based on a microscopic model of gene regulation that incorporates stochastic effects. In particular, we show how operator strength and operator multiplicity affect this variability. We examine different modes of transcription factor binding to complex promoters (cooperative, independent, simultaneous) and how each of these affects the level of variability in transcriptional output from cell-to-cell. We propose that direct comparison between in vivo single-cell experiments and theoretical predictions for the moments of the probability distribution of mRNA number per cell can be used to test kinetic models of gene regulation. The emphasis of the discussion is on prokaryotic gene regulation, but our analysis can be extended to eukaryotic cells as well. PMID:21390269
Evolutionary Relationships Based on Cellular Structure.
ERIC Educational Resources Information Center
Van Winkle, Lon J.
1979-01-01
This laboratory exercise integrates the topics of cell structure, classification of living organisms, and evolution. It is suitable for secondary or college biology courses and was used in an interdisciplinary science course for nonscience majors. (BB)
Metaresearch for Evaluating Reproducibility in Ecology and Evolution
Fidler, Fiona; Chee, Yung En; Wintle, Bonnie C.; Burgman, Mark A.; McCarthy, Michael A.; Gordon, Ascelin
2017-01-01
Abstract Recent replication projects in other disciplines have uncovered disturbingly low levels of reproducibility, suggesting that those research literatures may contain unverifiable claims. The conditions contributing to irreproducibility in other disciplines are also present in ecology. These include a large discrepancy between the proportion of “positive” or “significant” results and the average statistical power of empirical research, incomplete reporting of sampling stopping rules and results, journal policies that discourage replication studies, and a prevailing publish-or-perish research culture that encourages questionable research practices. We argue that these conditions constitute sufficient reason to systematically evaluate the reproducibility of the evidence base in ecology and evolution. In some cases, the direct replication of ecological research is difficult because of strong temporal and spatial dependencies, so here, we propose metaresearch projects that will provide proxy measures of reproducibility. PMID:28596617
An Agent-Based Dynamic Model for Analysis of Distributed Space Exploration Architectures
NASA Astrophysics Data System (ADS)
Sindiy, Oleg V.; DeLaurentis, Daniel A.; Stein, William B.
2009-07-01
A range of complex challenges, but also potentially unique rewards, underlie the development of exploration architectures that use a distributed, dynamic network of resources across the solar system. From a methodological perspective, the prime challenge is to systematically model the evolution (and quantify comparative performance) of such architectures, under uncertainty, to effectively direct further study of specialized trajectories, spacecraft technologies, concept of operations, and resource allocation. A process model for System-of-Systems Engineering is used to define time-varying performance measures for comparative architecture analysis and identification of distinguishing patterns among interoperating systems. Agent-based modeling serves as the means to create a discrete-time simulation that generates dynamics for the study of architecture evolution. A Solar System Mobility Network proof-of-concept problem is introduced representing a set of longer-term, distributed exploration architectures. Options within this set revolve around deployment of human and robotic exploration and infrastructure assets, their organization, interoperability, and evolution, i.e., a system-of-systems. Agent-based simulations quantify relative payoffs for a fully distributed architecture (which can be significant over the long term), the latency period before they are manifest, and the up-front investment (which can be substantial compared to alternatives). Verification and sensitivity results provide further insight on development paths and indicate that the framework and simulation modeling approach may be useful in architectural design of other space exploration mass, energy, and information exchange settings.
Evolution of the Busbar Structure in Large-Scale Aluminum Reduction Cells
NASA Astrophysics Data System (ADS)
Zhang, Hongliang; Liang, Jinding; Li, Jie; Sun, Kena; Xiao, Jin
2017-02-01
Studies of magnetic field and magneto-hydro-dynamics are regarded as the foundation for the development of large-scale aluminum reduction cells, while due to the direct relationship between the busbar configuration and magnetic compensation, the actual key content is the configuration of the busbar. As the line current has been increased from 160 kA to 600 kA, the configuration of the busbar was becoming more complex. To summarize and explore the evolution of busbar configuration in aluminum reduction cells, this paper has reviewed various representative large-scale pre-baked aluminum reduction cell busbar structures, such as end-to-end potlines, side-by-side potlines and external compensation current. The advantages and disadvantages in the magnetic distribution or technical specifications have also been introduced separately, especially for the configurations of the mainstream 400-kA potlines. In the end, the development trends of the bus structure configuration were prospected, based on the recent successful applications of super-scale cell busbar structures in China (500-600 kA).
Novel catalysts and photoelectrochemical system for solar fuel production
NASA Astrophysics Data System (ADS)
Zhang, Yan
Solar fuel production from abundant raw chemicals such as CO2 and water is highly desired as a clean renewable energy solution for the future. Developing photoelectrochemical cells is viewed as a promising approach to realize this energy conversion and storage process. Efficient and robust oxygen evolution catalyst made from non-precious materials remains a major challenge for such a system. This thesis basically consists of three parts of work, including studies on enhancing the photocatalytic oxygen evolution activity of cobalt-based spinel nanoparticles by manganese3+ substitution, in situ formation of cobalt oxide nanocubanes as highly active catalyst for photocatalytic oxygen evolution reaction, and development of a photoanode-driven photoelectrochemical cell for CO2 reduction with water. The first part of this thesis work devotes efforts in the development and study on cobalt and other transition metal oxide based oxygen evolution catalyst. Photocatalytic oxygen evolution is a critical step for solar fuel production from abundant sources. It poses a significant challenge because it requires an efficient catalyst to bridge the one-electron photon capture process with the four-electron oxygen reaction. Among all the metal oxides, Co3O4 spinel exhibits a high activity as an oxygen evolution catalyst. The results of this work demonstrate that the photocatalytic oxygen evolution activity of Co3O4 spinel can be further enhanced by substituting Co with Mn in the spinel structure. Using a facile hydrothermal approach, Co3O4 spinel nanoparticles as well as Mn-substituted and Ni-substituted Co3O4 spinel nanoparticles with a typical particle size of 5-7 nm were successfully synthesized. The morphology and crystal structures of the as-synthesized nanoparticle catalysts have been carefully examined using various structural characterization techniques, including powder x-ray diffraction (PXRD), transmission electron microscope (TEM), gas adsorption, and x-ray absorption spectroscopy (XAS). The photocatalytic activities of as-made nanoparticles were investigated using a well-studied visible light driven [Ru(bpy)3]2+-persulfate system. In both Clark electrode and reactor/gas chromatography (GC) systems, Mn-substituted Co3O 4 nanoparticles exhibited the highest turnover frequency (TOF) among all the three kinds of catalysts. The data presented in this paper suggest that the photocatalytic oxygen evolution activity of Co3O 4 spinel catalyst can be further enhanced by Mn3+ substitution at the octahedral sites. The second part of this piece of work was carried out to further investigate cobalt oxide based photocatalytic oxygen evolution catalyst. A new strategy was developed to synthesize nonsupported cobalt oxide nanocubanes through an in situ phase transformation mechanism using a layered Co(OH)(OCH3) precursor. Under sonication, the precursor was exfoliated and transformed into cobalt oxide nanocubanes in the presence of NaHCO 3-Na2SiF6 buffer solution. The resulting cobalt catalyst with an average particle size less than 2 nm exhibited a turnover frequency of 0.0023 per second per cobalt in photocatalytic oxygen evolution reaction. X-ray absorption results suggested that a unique nanocubane structure, where 13 cobalt atoms fully coordinated with oxygen atoms and hydroxide groups in an octahedral arrangement to form 8 Co4O4 cubanes, may be responsible for the exceptionally high oxygen evolution catalysis activity. This thesis work is completed with the development of a photoanode-driven photoelectrochemical cell for CO2 reduction. A NiOx decorated Si photoanode and nanoporous Ag cathode were employed. With an external bias of 2.0 V, a current density at cathode of 10 mA/cm2 and Faradaic efficiency of 70% for CO2 to CO was achieved. Compared to a normal electrochemical cell, the photoelectrochemical cell saves 0.4 V electrical energy by absorbing photo-energy. In addition, post-test photoanodes were carefully characterized by SEM, XAS, and XPS analysis.
Modeling evolution of crosstalk in noisy signal transduction networks
NASA Astrophysics Data System (ADS)
Tareen, Ammar; Wingreen, Ned S.; Mukhopadhyay, Ranjan
2018-02-01
Signal transduction networks can form highly interconnected systems within cells due to crosstalk between constituent pathways. To better understand the evolutionary design principles underlying such networks, we study the evolution of crosstalk for two parallel signaling pathways that arise via gene duplication. We use a sequence-based evolutionary algorithm and evolve the network based on two physically motivated fitness functions related to information transmission. We find that one fitness function leads to a high degree of crosstalk while the other leads to pathway specificity. Our results offer insights on the relationship between network architecture and information transmission for noisy biomolecular networks.
Use of the "Tree" Analogy in Evolution Teaching by Biology Teachers
ERIC Educational Resources Information Center
Marcelos, Maria Fatima; Nagem, Ronaldo Luiz
2012-01-01
This work discusses the use of Darwin's "Tree of Life" as a didactic analogy and metaphor in teaching evolution. It investigates whether biology teachers of pupils from 17 to 18 years old know Darwin's text "Tree of Life". In addition, it examines whether those teachers systematically employ either the analogies present in that…
NASA Astrophysics Data System (ADS)
Shank, T. M.; German, C.; Machado, C.; Bowen, A.; Drazen, J.; Yancey, P.; Jamieson, A.; Rowden, A.; Clark, M.; Heyl, T.; Mayor, D.; Piertney, S.; Ruhl, H.
2018-05-01
Key questions on life’s evolution are being pursued in Earth’s hadal ocean, Earth’s only analog to Europa’s ocean. A recent WHOI-JPL partnership is developing an armada of autonomous underwater drone vehicles to explore of Earth’s and Europa’s oceans.
NASA Astrophysics Data System (ADS)
Beirle, Steffen; Lampel, Johannes; Wang, Yang; Mies, Kornelia; Dörner, Steffen; Grossi, Margherita; Loyola, Diego; Dehn, Angelika; Danielczok, Anja; Schröder, Marc; Wagner, Thomas
2018-03-01
We present time series of the global distribution of water vapor columns over more than 2 decades based on measurements from the satellite instruments GOME, SCIAMACHY, and GOME-2 in the red spectral range. A particular focus is the consistency amongst the different sensors to avoid jumps from one instrument to another. This is reached by applying robust and simple retrieval settings consistently. Potentially systematic effects due to differences in ground pixel size are avoided by merging SCIAMACHY and GOME-2 observations to GOME spatial resolution, which also allows for a consistent treatment of cloud effects. In addition, the GOME-2 swath is reduced to that of GOME and SCIAMACHY to have consistent viewing geometries.Remaining systematic differences between the different sensors are investigated during overlap periods and are corrected for in the homogenized time series. The resulting Climate
product v2.2 (https://doi.org/10.1594/WDCC/GOME-EVL_water_vapor_clim_v2.2) allows the study of the temporal evolution of water vapor over the last 20 years on a global scale.
Change detection of polarimetric SAR images based on the KummerU Distribution
NASA Astrophysics Data System (ADS)
Chen, Quan; Zou, Pengfei; Li, Zhen; Zhang, Ping
2014-11-01
In the society of PolSAR image segmentation, change detection and classification, the classical Wishart distribution has been used for a long time, but it especially suit to low-resolution SAR image, because in traditional sensors, only a small number of scatterers are present in each resolution cell. With the improving of SAR systems these years, the classical statistical models can therefore be reconsidered for high resolution and polarimetric information contained in the images acquired by these advanced systems. In this study, SAR image segmentation algorithm based on level-set method, added with distance regularized level-set evolution (DRLSE) is performed using Envisat/ASAR single-polarization data and Radarsat-2 polarimetric images, respectively. KummerU heterogeneous clutter model is used in the later to overcome the homogeneous hypothesis at high resolution cell. An enhanced distance regularized level-set evolution (DRLSE-E) is also applied in the later, to ensure accurate computation and stable level-set evolution. Finally, change detection based on four polarimetric Radarsat-2 time series images is carried out at Genhe area of Inner Mongolia Autonomous Region, NorthEastern of China, where a heavy flood disaster occurred during the summer of 2013, result shows the recommend segmentation method can detect the change of watershed effectively.
A Mechanistic Thermal Fatigue Model for SnAgCu Solder Joints
NASA Astrophysics Data System (ADS)
Borgesen, Peter; Wentlent, Luke; Hamasha, Sa'd.; Khasawneh, Saif; Shirazi, Sam; Schmitz, Debora; Alghoul, Thaer; Greene, Chris; Yin, Liang
2018-02-01
The present work offers both a complete, quantitative model and a conservative acceleration factor expression for the life span of SnAgCu solder joints in thermal cycling. A broad range of thermal cycling experiments, conducted over many years, has revealed a series of systematic trends that are not compatible with common damage functions or constitutive relations. Complementary mechanical testing and systematic studies of the evolution of the microstructure and damage have led to a fundamental understanding of the progression of thermal fatigue and failure. A special experiment was developed to allow the effective deconstruction of conventional thermal cycling experiments and the finalization of our model. According to this model, the evolution of damage and failure in thermal cycling is controlled by a continuous recrystallization process which is dominated by the coalescence and rotation of dislocation cell structures continuously added to during the high-temperature dwell. The dominance of this dynamic recrystallization contribution is not consistent with the common assumption of a correlation between the number of cycles to failure and the total work done on the solder joint in question in each cycle. It is, however, consistent with an apparent dependence on the work done during the high-temperature dwell. Importantly, the onset of this recrystallization is delayed by pinning on the Ag3Sn precipitates until these have coarsened sufficiently, leading to a model with two terms where one tends to dominate in service and the other in accelerated thermal cycling tests. Accumulation of damage under realistic service conditions with varying dwell temperatures and times is also addressed.
EVOLUTION OF NEAR-SURFACE FLOWS INFERRED FROM HIGH-RESOLUTION RING-DIAGRAM ANALYSIS
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bogart, Richard S.; Baldner, Charles S.; Basu, Sarbani
2015-07-10
Ring-diagram analysis of acoustic waves observed at the photosphere can provide a relatively robust determination of the sub-surface flows at a particular time under a particular region. The depth of penetration of the waves is related to the size of the region, hence the depth extent of the measured flows is inversely proportional to the spatial resolution. Most ring-diagram analysis has focused on regions of extent ∼15° (180 Mm) or more in order to provide reasonable mode sets for inversions. Helioseismic and Magnetic Imager (HMI) data analysis also provides a set of ring fit parameters on a scale three timesmore » smaller. These provide flow estimates for the outer 1% (7 Mm) of the Sun only, with very limited depth resolution, but with spatial resolution adequate to map structures potentially associated with the belts and regions of magnetic activity. There are a number of systematic effects affecting the determination of flows from a local helioseismic analysis of regions over different parts of the observable disk, and not all of them are well understood. In this study we characterize those systematic effects with higher spatial resolution so that they may be accounted for more effectively in mapping the temporal and spatial evolution of the flows. Leaving open the question of the mean structure of the global meridional circulation and the differential rotation, we describe the near-surface flow anomalies in time and latitude corresponding to the torsional oscillation pattern in differential rotation and analogous patterns in the meridional cell structure as observed by the Solar Dynamics Observatory/HMI.« less
Symbiosis in cell evolution: Life and its environment on the early earth
NASA Technical Reports Server (NTRS)
Margulis, L.
1981-01-01
The book treats cell evolution from the viewpoint of the serial endosymbiosis theory of the origin of organelles. Following a brief outline of the symbiotic theory, which holds that eukaryotes evolved by the association of free-living bacteria with a host prokaryote, the diversity of life is considered, and five kingdoms of organisms are distinguished: the prokaryotic Monera and the eukaryotic Protoctista, Animalia, Fungi and Plantae. Symbiotic and traditional direct filiation theories of cell evolution are compared. Recent observations of cell structure and biochemistry are reviewed in relation to early cell evolution, with attention given to the geological context for the origin of eukaryotic cells, the origin of major bacterial anaerobic pathways, the relationship between aerobic metabolism and atmospheric oxygen, criteria for distinguishing symbiotic organelles from those that originated by differentiation, and the major classes of eukaryotic organelles: mitochondria, cilia, microtubules, the mitotic and meiotic apparatuses, and pastids. Cell evolution during the Phanerozoic is also discussed with emphasis on the effects of life on the biosphere
The evolution of the animals: introduction to a Linnean tercentenary celebration.
Telford, Maximilian J; Littlewood, D Timothy J
2008-04-27
Celebrating 300 years since the birth of Carl Linnaeus (1707-1778), a meeting was held in June 2007 to review recent progress made in understanding the origins and evolutionary radiation of the animals. The year 2008 celebrates the 250th anniversary of the publication of the 10th edition of Linnaeus' Systema Naturae, generally considered to be the starting point of zoological nomenclature. With subsequent advances in comparative taxonomic and systematic studies, Darwin's discovery of evolution by natural selection, the birth of phylogenetic systematics, and the wider interest in biodiversity, it is salutary to consider that many of the major advances in our understanding of animal evolution have been made in recent years. Phylogenetic systematics, drawing from evidence provided by genotype, phenotype and an understanding of the link between them through comparative embryological and evolutionary developmental studies, has provided a wide consensus of the major branching patterns of the tree of life. More importantly, the integrated approaches discussed in the 16 contributions to this volume highlight the identity and nature of problematic taxa, the missing data, errors in existing analytical procedures and the promise of a wealth of additional characters from genomes that need to be accumulated and assessed in providing a definitive Systema Naturae.
A noise model for the evaluation of defect states in solar cells
Landi, G.; Barone, C.; Mauro, C.; Neitzert, H. C.; Pagano, S.
2016-01-01
A theoretical model, combining trapping/detrapping and recombination mechanisms, is formulated to explain the origin of random current fluctuations in silicon-based solar cells. In this framework, the comparison between dark and photo-induced noise allows the determination of important electronic parameters of the defect states. A detailed analysis of the electric noise, at different temperatures and for different illumination levels, is reported for crystalline silicon-based solar cells, in the pristine form and after artificial degradation with high energy protons. The evolution of the dominating defect properties is studied through noise spectroscopy. PMID:27412097
NASA Astrophysics Data System (ADS)
Perry, Dan; Nakamoto, Mark; Verghese, Nishath; Hurat, Philippe; Rouse, Rich
2007-03-01
Model-based hotspot detection and silicon-aware parametric analysis help designers optimize their chips for yield, area and performance without the high cost of applying foundries' recommended design rules. This set of DFM/ recommended rules is primarily litho-driven, but cannot guarantee a manufacturable design without imposing overly restrictive design requirements. This rule-based methodology of making design decisions based on idealized polygons that no longer represent what is on silicon needs to be replaced. Using model-based simulation of the lithography, OPC, RET and etch effects, followed by electrical evaluation of the resulting shapes, leads to a more realistic and accurate analysis. This analysis can be used to evaluate intelligent design trade-offs and identify potential failures due to systematic manufacturing defects during the design phase. The successful DFM design methodology consists of three parts: 1. Achieve a more aggressive layout through limited usage of litho-related recommended design rules. A 10% to 15% area reduction is achieved by using more aggressive design rules. DFM/recommended design rules are used only if there is no impact on cell size. 2. Identify and fix hotspots using a model-based layout printability checker. Model-based litho and etch simulation are done at the cell level to identify hotspots. Violations of recommended rules may cause additional hotspots, which are then fixed. The resulting design is ready for step 3. 3. Improve timing accuracy with a process-aware parametric analysis tool for transistors and interconnect. Contours of diffusion, poly and metal layers are used for parametric analysis. In this paper, we show the results of this physical and electrical DFM methodology at Qualcomm. We describe how Qualcomm was able to develop more aggressive cell designs that yielded a 10% to 15% area reduction using this methodology. Model-based shape simulation was employed during library development to validate architecture choices and to optimize cell layout. At the physical verification stage, the shape simulator was run at full-chip level to identify and fix residual hotspots on interconnect layers, on poly or metal 1 due to interaction between adjacent cells, or on metal 1 due to interaction between routing (via and via cover) and cell geometry. To determine an appropriate electrical DFM solution, Qualcomm developed an experiment to examine various electrical effects. After reporting the silicon results of this experiment, which showed sizeable delay variations due to lithography-related systematic effects, we also explain how contours of diffusion, poly and metal can be used for silicon-aware parametric analysis of transistors and interconnect at the cell-, block- and chip-level.
Gautier, Hélène; Vavasseur, Alain; Gans, Pierre; Lascève, Gérard
1991-01-01
A mass spectrometric method combining 16O/18O and 12C/13C isotopes was used to quantify the unidirectional fluxes of O2 and CO2 during a dark to light transition for guard cell protoplasts and mesophyll cell protoplasts of Commelina communis L. In darkness, O2 uptake and CO2 evolution were similar on a protein basis. Under light, guard cell protoplasts evolved O2 (61 micromoles of O2 per milligram of chlorophyll per hour) almost at the same rate as mesophyll cell protoplasts (73 micromoles of O2 per milligram of chlorophyll per hour). However, carbon assimilation was totally different. In contrast with mesophyll cell protoplasts, guard cell protoplasts were able to fix CO2 in darkness at a rate of 27 micromoles of CO2 per milligram of chlorophyll per hour, which was increased by 50% in light. At the onset of light, a delay observed for guard cell protoplasts between O2 evolution and CO2 fixation and a time lag before the rate of saturation suggested a carbon metabolism based on phosphoenolpyruvate carboxylase activity. Under light, CO2 evolution by guard cell protoplasts was sharply decreased (37%), while O2 uptake was slowly inhibited (14%). A control of mitochondrial activity by guard cell chloroplasts under light via redox equivalents and ATP transfer in the cytosol is discussed. From this study on protoplasts, we conclude that the energy produced at the chloroplast level under light is not totally used for CO2 assimilation and may be dissipated for other purposes such as ion uptake. PMID:16668030
Deep phylogeny and evolution of sponges (phylum Porifera).
Wörheide, G; Dohrmann, M; Erpenbeck, D; Larroux, C; Maldonado, M; Voigt, O; Borchiellini, C; Lavrov, D V
2012-01-01
Sponges (phylum Porifera) are a diverse taxon of benthic aquatic animals of great ecological, commercial, and biopharmaceutical importance. They are arguably the earliest-branching metazoan taxon, and therefore, they have great significance in the reconstruction of early metazoan evolution. Yet, the phylogeny and systematics of sponges are to some extent still unresolved, and there is an on-going debate about the exact branching pattern of their main clades and their relationships to the other non-bilaterian animals. Here, we review the current state of the deep phylogeny of sponges. Several studies have suggested that sponges are paraphyletic. However, based on recent phylogenomic analyses, we suggest that the phylum Porifera could well be monophyletic, in accordance with cladistic analyses based on morphology. This finding has many implications for the evolutionary interpretation of early animal traits and sponge development. We further review the contribution that mitochondrial genes and genomes have made to sponge phylogenetics and explore the current state of the molecular phylogenies of the four main sponge lineages (Classes), that is, Demospongiae, Hexactinellida, Calcarea, and Homoscleromorpha, in detail. While classical systematic systems are largely congruent with molecular phylogenies in the class Hexactinellida and in certain parts of Demospongiae and Homoscleromorpha, the high degree of incongruence in the class Calcarea still represents a challenge. We highlight future areas of research to fill existing gaps in our knowledge. By reviewing sponge development in an evolutionary and phylogenetic context, we support previous suggestions that sponge larvae share traits and complexity with eumetazoans and that the simple sedentary adult lifestyle of sponges probably reflects some degree of secondary simplification. In summary, while deep sponge phylogenetics has made many advances in the past years, considerable efforts are still required to achieve a comprehensive understanding of the relationships among and within the main sponge lineages to fully appreciate the evolution of this extraordinary metazoan phylum. Copyright © 2012 Elsevier Ltd. All rights reserved.
García-Cabezas, Miguel Á.; John, Yohan J.; Barbas, Helen; Zikopoulos, Basilis
2016-01-01
The estimation of the number or density of neurons and types of glial cells and their relative proportions in different brain areas are at the core of rigorous quantitative neuroanatomical studies. Unfortunately, the lack of detailed, updated, systematic and well-illustrated descriptions of the cytology of neurons and glial cell types, especially in the primate brain, makes such studies especially demanding, often limiting their scope and broad use. Here, following an extensive analysis of histological materials and the review of current and classical literature, we compile a list of precise morphological criteria that can facilitate and standardize identification of cells in stained sections examined under the microscope. We describe systematically and in detail the cytological features of neurons and glial cell types in the cerebral cortex of the macaque monkey and the human using semithin and thick sections stained for Nissl. We used this classical staining technique because it labels all cells in the brain in distinct ways. In addition, we corroborate key distinguishing characteristics of different cell types in sections immunolabeled for specific markers counterstained for Nissl and in ultrathin sections processed for electron microscopy. Finally, we summarize the core features that distinguish each cell type in easy-to-use tables and sketches, and structure these key features in an algorithm that can be used to systematically distinguish cellular types in the cerebral cortex. Moreover, we report high inter-observer algorithm reliability, which is a crucial test for obtaining consistent and reproducible cell counts in unbiased stereological studies. This protocol establishes a consistent framework that can be used to reliably identify and quantify cells in the cerebral cortex of primates as well as other mammalian species in health and disease. PMID:27847469
Biosensor-driven adaptive laboratory evolution of l-valine production in Corynebacterium glutamicum.
Mahr, Regina; Gätgens, Cornelia; Gätgens, Jochem; Polen, Tino; Kalinowski, Jörn; Frunzke, Julia
2015-11-01
Adaptive laboratory evolution has proven a valuable strategy for metabolic engineering. Here, we established an experimental evolution approach for improving microbial metabolite production by imposing an artificial selective pressure on the fluorescent output of a biosensor using fluorescence-activated cell sorting. Cells showing the highest fluorescent output were iteratively isolated and (re-)cultivated. The L-valine producer Corynebacterium glutamicum ΔaceE was equipped with an L-valine-responsive sensor based on the transcriptional regulator Lrp of C. glutamicum. Evolved strains featured a significantly higher growth rate, increased L-valine titers (~25%) and a 3-4-fold reduction of by-product formation. Genome sequencing resulted in the identification of a loss-of-function mutation (UreD-E188*) in the gene ureD (urease accessory protein), which was shown to increase L-valine production by up to 100%. Furthermore, decreased L-alanine formation was attributed to a mutation in the global regulator GlxR. These results emphasize biosensor-driven evolution as a straightforward approach to improve growth and productivity of microbial production strains. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.
A numerical analysis of the performance of unpumped SBE 41 sensors at low flushing rates
NASA Astrophysics Data System (ADS)
Alvarez, A.
2018-05-01
The thermal and hydrodynamic response of a Sea-Bird unpumped CTD SBE 41, is numerically modeled to assess the biases occurring at the slow flushing rates typical of glider operations. Based on symmetry considerations, the sensor response is approximated by coupling the incompressible Navier-Stokes and the thermal advection-diffusion equations in two dimensions. Numerical results illustrate three regimes in the thermal response of the SBE 41 sensor, when crossing water layers with different thermal signatures. A linear decay in time of the bulk temperature of the conductivity cell is initially found. This is induced by the transit of the inflow through the conductivity cell in the form of a relatively narrow jet. Water masses with new thermal signatures do not immediately fill the sensor chambers, where the cross-section widens. Thermal equilibrium of these water masses is then achieved, in a second regime, via a cross-flow thermal diffusion between the boundary of the jet and the walls. Consequently, the evolution of the bulk temperature scales with the square root of time. In a third regime, the evolution of the bulk temperature depends on the thermal gradient between the fluid and the coating material. This results on an exponential decay of the bulk temperature with time. A comprehensive analytical model of the time evolution of the bulk temperature inside a cell is proposed based on these results.
Cell Adhesion on Surface-Functionalized Magnesium.
Wagener, Victoria; Schilling, Achim; Mainka, Astrid; Hennig, Diana; Gerum, Richard; Kelch, Marie-Luise; Keim, Simon; Fabry, Ben; Virtanen, Sannakaisa
2016-05-18
The biocompatibility of commercially pure magnesium-based (cp Mg) biodegradable implants is compromised of strong hydrogen evolution and surface alkalization due to high initial corrosion rates of cp Mg in the physiological environment. To mitigate this problem, the addition of corrosion-retarding alloying elements or coating of implant surfaces has been suggested. In the following work, we explored the effect of organic coatings on long-term cell growth. cp Mg was coated with aminopropyltriehtoxysilane + vitamin C (AV), carbonyldiimidazole (CDI), or stearic acid (SA). All three coatings have been previously suggested to reduce initial corrosion and to enhance protein adsorption and hence cell adhesion on magnesium surfaces. Endothelial cells (DH1+/+) and osteosarcoma cells (MG63) were cultured on coated samples for up to 20 days. To quantify Mg corrosion, electrochemical impedance spectroscopy (EIS) was measured after 1, 3, and 5 days of cell culture. We also investigated the speed of initial cell spreading after seeding using fluorescently labeled fibroblasts (NIH/3T3). Hydrogen evolution after contact with cell culture medium was markedly decreased on AV- and SA-coated Mg compared to uncoated Mg. These coatings also showed improved cell adhesion and spreading after 24 h of culture comparable to tissue-treated plastic surfaces. On AV-coated cp Mg, a confluent layer of endothelial cells formed after 5 days and remained intact for up to 20 days. Together, these data demonstrate that surface coating with AV is a viable strategy for improving long-term biocompatibility of cp Mg-based implants. EIS measurements confirmed that the presence of a confluent cell layer increased the corrosion resistance.
Driessen, Elisabeth J; Peeters, Marieke E; Bongers, Bart C; Maas, Huub A; Bootsma, Gerbern P; van Meeteren, Nico L; Janssen-Heijnen, Maryska L
2017-06-01
This systematic review aimed to examine physical fitness, adherence, treatment tolerance, and recovery for (p)rehabilitation including a home-based component for patients with non-small cell lung cancer (NSCLC). PRISMA and Cochrane guidelines were followed. Studies describing (home-based) prehabilitation or rehabilitation in patients with NSCLC were included from four databases (January 2000-April 2016, N=11). Nine of ten rehabilitation studies and one prehabilitation study (437 NSCLC patients, mean age 59-72 years) showed significantly or clinically relevant improved physical fitness. Three (27%) assessed home-based training and eight (73%) combined training at home, inhospital (intramural) and/or at the physiotherapy practice/department (extramural). Six (55%) applied supervision of home-based components, and four (36%) a personalized training program. Adherence varied strongly (9-125% for exercises, 50-100% for patients). Treatment tolerance and recovery were heterogeneously reported. Although promising results of (p)rehabilitation for improving physical fitness were found (especially in case of supervision and personalization), adequately powered studies for home-based (p)rehabilitation are needed. Copyright © 2017 Elsevier B.V. All rights reserved.
Reassessment of roles of oxygen and ultraviolet light in Precambrian evolution
NASA Technical Reports Server (NTRS)
Margulis, L.; Rambler, M.; Walker, J. C. G.
1976-01-01
It is argued that the transition to an oxidizing atmosphere preceded the origin of eukaryotic cells, which in turn must have preceded the origin of metazoa. Moreover, the number of methods by which organisms can protect themselves from harmful UV radiation is sufficiently large to suggest that solar UV, even when the atmosphere was anaerobic, was not such as to control the distribution and diversification of life. An alternative explanation for the late and sudden appearance of metazoa in lower Cambrian sediments is proposed, which is related to the mechanisms by which fully mature eukaryotic cells probably originated. There was probably a protracted evolution of modern genetic systems based on mitosis in cells which acquired organelles (e.g., plastids and mitochondria) by hereditary endosymbiosis. The origin of hard parts underlies the Cambrian explosion of metazoans.
Aptamers in Diagnostics and Treatment of Viral Infections
Wandtke, Tomasz; Woźniak, Joanna; Kopiński, Piotr
2015-01-01
Aptamers are in vitro selected DNA or RNA molecules that are capable of binding a wide range of nucleic and non-nucleic acid molecules with high affinity and specificity. They have been conducted through the process known as SELEX (Systematic Evolution of Ligands by Exponential Enrichment). It serves to reach specificity and considerable affinity to target molecules, including those of viral origin, both proteins and nucleic acids. Properties of aptamers allow detecting virus infected cells or viruses themselves and make them competitive to monoclonal antibodies. Specific aptamers can be used to interfere in each stage of the viral replication cycle and also inhibit its penetration into cells. Many current studies have reported possible application of aptamers as a treatment or diagnostic tool in viral infections, e.g., HIV (Human Immunodeficiency Virus), HBV (Hepatitis B Virus), HCV (Hepatitis C Virus), SARS (Severe Acute Respiratory Syndrome), H5N1 avian influenza and recently spread Ebola. This review presents current developments of using aptamers in the diagnostics and treatment of viral diseases. PMID:25690797
What's new in skin cancer? An analysis of guidelines and systematic reviews published in 2008-2009.
Macbeth, A E; Grindlay, D J C; Williams, H C
2011-07-01
This review summarizes clinically important findings from 17 systematic reviews and 2 guidelines on skin cancer indexed between April 2008 and April 2009. Melanoma primary-prevention measures, such as education, are more likely to be successful in younger children than adolescents, and general population screening for melanoma by whole-body examination is not currently supported by the evidence. A large systematic review of melanoma and pregnancy concluded that pregnancy does not affect prognosis. Two systematic reviews imply that sunburn later in life also increases the risk of melanoma, and that it is just as important as sunburn early in life. Three systematic reviews discussed the role of positron emission tomography and sentinel lymph-node biopsy for melanoma staging, but produced conflicting results. Superior diagnostic accuracy of dermatoscopy over naked-eye examination for melanoma was found in one review, while a second implied nonsignificantly higher sensitivity of computer-based diagnostic methods over dermatoscopy for melanoma but with reduced specificity. There were no identified randomized controlled trials of treatments for unresectable recurrent melanoma, and a review of immunotherapy with vaccines for melanoma failed to prove improved overall and disease-free survival. Guidelines for the management of basal cell carcinoma call for risk stratification, based on numerous factors including tumour size, site and histological subtype. Squamous cell carcinoma of the ear has been shown to spread to regional lymph nodes more commonly than to other sites, and may be predicted by depth of invasion, tumour size, cellular differentiation and completeness of excision. © The Author(s). CED © 2011 British Association of Dermatologists.
Systematic gene tagging using CRISPR/Cas9 in human stem cells to illuminate cell organization
Roberts, Brock; Haupt, Amanda; Tucker, Andrew; Grancharova, Tanya; Arakaki, Joy; Fuqua, Margaret A.; Nelson, Angelique; Hookway, Caroline; Ludmann, Susan A.; Mueller, Irina A.; Yang, Ruian; Horwitz, Rick; Rafelski, Susanne M.; Gunawardane, Ruwanthi N.
2017-01-01
We present a CRISPR/Cas9 genome-editing strategy to systematically tag endogenous proteins with fluorescent tags in human induced pluripotent stem cells (hiPSC). To date, we have generated multiple hiPSC lines with monoallelic green fluorescent protein tags labeling 10 proteins representing major cellular structures. The tagged proteins include alpha tubulin, beta actin, desmoplakin, fibrillarin, nuclear lamin B1, nonmuscle myosin heavy chain IIB, paxillin, Sec61 beta, tight junction protein ZO1, and Tom20. Our genome-editing methodology using Cas9/crRNA ribonuclear protein and donor plasmid coelectroporation, followed by fluorescence-based enrichment of edited cells, typically resulted in <0.1–4% homology-directed repair (HDR). Twenty-five percent of clones generated from each edited population were precisely edited. Furthermore, 92% (36/39) of expanded clonal lines displayed robust morphology, genomic stability, expression and localization of the tagged protein to the appropriate subcellular structure, pluripotency-marker expression, and multilineage differentiation. It is our conclusion that, if cell lines are confirmed to harbor an appropriate gene edit, pluripotency, differentiation potential, and genomic stability are typically maintained during the clonal line–generation process. The data described here reveal general trends that emerged from this systematic gene-tagging approach. Final clonal lines corresponding to each of the 10 cellular structures are now available to the research community. PMID:28814507
Wei, Guang-Feng
2015-01-01
The restructuring of nanoparticles at the in situ condition is a common but complex phenomenon in nanoscience. Here, we present the first systematic survey on the structure dynamics and its catalytic consequence for hydrogen evolution reaction (HER) on Pt nanoparticles, as represented by a magic number Pt44 octahedron (∼1 nm size). Using a first principles calculation based global structure search method, we stepwise follow the significant nanoparticle restructuring under HER conditions as driven by thermodynamics to expose {100} facets, and reveal the consequent large activity enhancement due to the marked increase of the concentration of the active site, being identified to be apex atoms. The enhanced kinetics is thus a “byproduct” of the thermodynamical restructuring. Based on the results, the best Pt catalyst for HER is predicted to be ultrasmall Pt particles without core atoms, a size below ∼20 atoms. PMID:29560237
Tonelli, R R; Colli, W; Alves, M J M
2012-01-01
Parasite infections are largely dependent on interactions between pathogen and different host cell populations to guarantee a successful infectious process. This is particularly true for obligatory intracellular parasites as Plasmodium, Toxoplasma, and Leishmania, to name a few. Adhesion to and entry into the cell are essential steps requiring specific parasite and host cell molecules. The large amount of possible involved molecules poses additional difficulties for their identification by the classical biochemical approaches. In this respect, the search for alternative techniques should be pursued. Among them two powerful methodologies can be employed, both relying upon the construction of highly diverse combinatorial libraries of peptides or oligonucleotides that randomly bind with high affinity to targets on the cell surface and are selectively displaced by putative ligands. These are, respectively, the peptide-based phage display and the oligonucleotide-based aptamer techniques. The phage display technique has been extensively employed for the identification of novel ligands in vitro and in vivo in different areas such as cancer, vaccine development, and epitope mapping. Particularly, phage display has been employed in the investigation of pathogen-host interactions. Although this methodology has been used for some parasites with encouraging results, in trypanosomatids its use is, as yet, scanty. RNA and DNA aptamers, developed by the SELEX process (Systematic Evolution of Ligands by Exponential Enrichment), were described over two decades ago and since then contributed to a large number of structured nucleic acids for diagnostic or therapeutic purposes or for the understanding of the cell biology. Similarly to the phage display technique scarce use of the SELEX process has been used in the probing of parasite-host interaction. In this review, an overall survey on the use of both phage display and aptamer technologies in different pathogenic organisms will be discussed. Using these techniques, recent results on the interaction of Trypanosoma cruzi with the host will be highlighted focusing on members of the 85 kDa protein family, a subset of the gp85/TS superfamily.
Classifying the evolutionary and ecological features of neoplasms.
Maley, Carlo C; Aktipis, Athena; Graham, Trevor A; Sottoriva, Andrea; Boddy, Amy M; Janiszewska, Michalina; Silva, Ariosto S; Gerlinger, Marco; Yuan, Yinyin; Pienta, Kenneth J; Anderson, Karen S; Gatenby, Robert; Swanton, Charles; Posada, David; Wu, Chung-I; Schiffman, Joshua D; Hwang, E Shelley; Polyak, Kornelia; Anderson, Alexander R A; Brown, Joel S; Greaves, Mel; Shibata, Darryl
2017-10-01
Neoplasms change over time through a process of cell-level evolution, driven by genetic and epigenetic alterations. However, the ecology of the microenvironment of a neoplastic cell determines which changes provide adaptive benefits. There is widespread recognition of the importance of these evolutionary and ecological processes in cancer, but to date, no system has been proposed for drawing clinically relevant distinctions between how different tumours are evolving. On the basis of a consensus conference of experts in the fields of cancer evolution and cancer ecology, we propose a framework for classifying tumours that is based on four relevant components. These are the diversity of neoplastic cells (intratumoural heterogeneity) and changes over time in that diversity, which make up an evolutionary index (Evo-index), as well as the hazards to neoplastic cell survival and the resources available to neoplastic cells, which make up an ecological index (Eco-index). We review evidence demonstrating the importance of each of these factors and describe multiple methods that can be used to measure them. Development of this classification system holds promise for enabling clinicians to personalize optimal interventions based on the evolvability of the patient's tumour. The Evo- and Eco-indices provide a common lexicon for communicating about how neoplasms change in response to interventions, with potential implications for clinical trials, personalized medicine and basic cancer research.
A self-triggered picoinjector in microfluidics
NASA Astrophysics Data System (ADS)
Yang, Yiming; Liu, Songsheng; Jia, Chunping; Mao, Hongju; Jin, Qinghui; Zhao, Jianlong; Zhou, Hongbo
2016-12-01
Droplet-based microfluidics has recently emerged as a potential platform for studies of single-cell, directed evolution, and genetic sequencing. In droplet-based microfluidics, adding reagents into drops is one of the most important functions. In this paper, we develop a new self-triggered picoinjector to add controlled volumes of reagent into droplets at kilohertz rates. In the picoinjector, the reagent injecting is triggered by the coming droplet itself, without needing a droplet detection module. Meanwhile, the dosing volume can be precisely controlled. These features make the system more practical and reliable. We expect the new picoinjector will find important applications of droplet-based microfluidics in automated biological assay, directed evolution, enzyme assay, and so on.
Inseparable tandem: evolution chooses ATP and Ca2+ to control life, death and cellular signalling
Verkhratsky, Alexei
2016-01-01
From the very dawn of biological evolution, ATP was selected as a multipurpose energy-storing molecule. Metabolism of ATP required intracellular free Ca2+ to be set at exceedingly low concentrations, which in turn provided the background for the role of Ca2+ as a universal signalling molecule. The early-eukaryote life forms also evolved functional compartmentalization and vesicle trafficking, which used Ca2+ as a universal signalling ion; similarly, Ca2+ is needed for regulation of ciliary and flagellar beat, amoeboid movement, intracellular transport, as well as of numerous metabolic processes. Thus, during evolution, exploitation of atmospheric oxygen and increasingly efficient ATP production via oxidative phosphorylation by bacterial endosymbionts were a first step for the emergence of complex eukaryotic cells. Simultaneously, Ca2+ started to be exploited for short-range signalling, despite restrictions by the preset phosphate-based energy metabolism, when both phosphates and Ca2+ interfere with each other because of the low solubility of calcium phosphates. The need to keep cytosolic Ca2+ low forced cells to restrict Ca2+ signals in space and time and to develop energetically favourable Ca2+ signalling and Ca2+ microdomains. These steps in tandem dominated further evolution. The ATP molecule (often released by Ca2+-regulated exocytosis) rapidly grew to be the universal chemical messenger for intercellular communication; ATP effects are mediated by an extended family of purinoceptors often linked to Ca2+ signalling. Similar to atmospheric oxygen, Ca2+ must have been reverted from a deleterious agent to a most useful (intra- and extracellular) signalling molecule. Invention of intracellular trafficking further increased the role for Ca2+ homeostasis that became critical for regulation of cell survival and cell death. Several mutually interdependent effects of Ca2+ and ATP have been exploited in evolution, thus turning an originally unholy alliance into a fascinating success story. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377729
Tang, Min; Zhao, Rui; van de Velde, Helgi; Tross, Jennifer G; Mitsiades, Constantine; Viselli, Suzanne; Neuwirth, Rachel; Esseltine, Dixie-Lee; Anderson, Kenneth; Ghobrial, Irene M; San Miguel, Jesús F; Richardson, Paul G; Tomasson, Michael H; Michor, Franziska
2016-08-15
Since the pioneering work of Salmon and Durie, quantitative measures of tumor burden in multiple myeloma have been used to make clinical predictions and model tumor growth. However, such quantitative analyses have not yet been performed on large datasets from trials using modern chemotherapy regimens. We analyzed a large set of tumor response data from three randomized controlled trials of bortezomib-based chemotherapy regimens (total sample size n = 1,469 patients) to establish and validate a novel mathematical model of multiple myeloma cell dynamics. Treatment dynamics in newly diagnosed patients were most consistent with a model postulating two tumor cell subpopulations, "progenitor cells" and "differentiated cells." Differential treatment responses were observed with significant tumoricidal effects on differentiated cells and less clear effects on progenitor cells. We validated this model using a second trial of newly diagnosed patients and a third trial of refractory patients. When applying our model to data of relapsed patients, we found that a hybrid model incorporating both a differentiation hierarchy and clonal evolution best explains the response patterns. The clinical data, together with mathematical modeling, suggest that bortezomib-based therapy exerts a selection pressure on myeloma cells that can shape the disease phenotype, thereby generating further inter-patient variability. This model may be a useful tool for improving our understanding of disease biology and the response to chemotherapy regimens. Clin Cancer Res; 22(16); 4206-14. ©2016 AACR. ©2016 American Association for Cancer Research.
Mn-53-Cr-53 Systematics of R-Chondrite NWA 753
NASA Technical Reports Server (NTRS)
Jogo, K.; Shih, C-Y.; Reese, Y. D.; Nyquist, L. E.
2006-01-01
Chondrules and chondrites are interpreted as objects formed in the early solar system, and it is important to study them in order to elucidate its evolution. Here, we report the study of the Mn-Cr systematics of the R-Chondrite NWA753 and compare the results to other chondrite data. The goal was to determine Cr isotopic and age variations among chondrite groups with different O-isotope signatures. The Mn-53-Cr-53 method as applied to individual chondrules [1] or bulk chondrites [2] is based on the assumption that 53Mn was initially homogeneously distributed in that portion the solar nebula where the chondrules and/or chondrites formed. However, different groups of chondrites formed from regions of different O-isotope compositions. So, different types of chondrites also may have had different initial Mn-53 abundances and/or Cr isotopic compositions. Thus, it is important to determine the Cr isotopic systematics among chondrites from various chondrite groups. We are studying CO-chondrite ALH83108 and Tagish Lake in addition to R-Chondrite NWA753. These meteorites have very distinct O-isotope compositions (Figure 1).
Wu, Weihua; Chen, Shiyu; Zhai, Jiwei; Liu, Xinyi; Lai, Tianshu; Song, Sannian; Song, Zhitang
2017-10-06
Superlattice-like Ge 50 Te 50 /Ge 8 Sb 92 (SLL GT/GS) thin film was systematically investigated for multi-level storage and ultra-fast switching phase-change memory application. In situ resistance measurement indicates that SLL GT/GS thin film exhibits two distinct resistance steps with elevated temperature. The thermal stability of the amorphous state and intermediate state were evaluated with the Kissinger and Arrhenius plots. The phase-structure evolution revealed that the amorphous SLL GT/GS thin film crystallized into rhombohedral Sb phase first, then the rhombohedral GeTe phase. The microstructure, layered structure, and interface stability of SLL GT/GS thin film was confirmed by using transmission electron microscopy. The transition speed of crystallization and amorphization was measured by the picosecond laser pump-probe system. The volume variation during the crystallization was obtained from x-ray reflectivity. Phase-change memory (PCM) cells based on SLL GT/GS thin film were fabricated to verify the multi-level switching under an electrical pulse as short as 30 ns. These results illustrate that the SLL GT/GS thin film has great potentiality in high-density and high-speed PCM applications.
On the relationship between the dynamic behavior and nanoscale staggered structure of the bone
NASA Astrophysics Data System (ADS)
Qwamizadeh, Mahan; Zhang, Zuoqi; Zhou, Kun; Zhang, Yong Wei
2015-05-01
Bone, a typical load-bearing biological material, composed of ordinary base materials such as organic protein and inorganic mineral arranged in a hierarchical architecture, exhibits extraordinary mechanical properties. Up to now, most of previous studies focused on its mechanical properties under static loading. However, failure of the bone occurs often under dynamic loading. An interesting question is: Are the structural sizes and layouts of the bone related or even adapted to the functionalities demanded by its dynamic performance? In the present work, systematic finite element analysis was performed on the dynamic response of nanoscale bone structures under dynamic loading. It was found that for a fixed mineral volume fraction and unit cell area, there exists a nanoscale staggered structure at some specific feature size and layout which exhibits the fastest attenuation of stress waves. Remarkably, these specific feature sizes and layouts are in excellent agreement with those experimentally observed in the bone at the same scale, indicating that the structural size and layout of the bone at the nanoscale are evolutionarily adapted to its dynamic behavior. The present work points out the importance of dynamic effect on the biological evolution of load-bearing biological materials.
Zheng, X; Hu, B; Gao, S X; Liu, D J; Sun, M J; Jiao, B H; Wang, L H
2015-07-01
Saxitoxin (STX), a member of the family of paralytic shellfish poisoning toxins, poses toxicological and ecotoxicological risks. To develop an analytical recognition element for STX, a DNA aptamer (APT(STX1)) was previously discovered via an iterative process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX) by Handy et al. Our study focused on generating an improved aptamer based on APT(STX1) through rational site-directed mutation and truncation. In this study, we generated the aptamer, M-30f, with a 30-fold higher affinity for STX compared with APT(STX1). The Kd value for M-30f was 133 nM, which was calculated by Bio-Layer Interferometry. After optimization, we detected and compared the interaction of STX with aptamers (APT(STX1) or M-30f) through several techniques (ELISA, cell bioassay, and mouse bioassay). Both aptamers' STX-binding ability was demonstrated in all three methods. Moreover, M-30f performs better than its parent sequence with higher suppressive activity against STX. As a molecular recognition element, M-30f has good prospects for practical application. Copyright © 2015 Elsevier Ltd. All rights reserved.
Student Visual Communication of Evolution
NASA Astrophysics Data System (ADS)
Oliveira, Alandeom W.; Cook, Kristin
2017-06-01
Despite growing recognition of the importance of visual representations to science education, previous research has given attention mostly to verbal modalities of evolution instruction. Visual aspects of classroom learning of evolution are yet to be systematically examined by science educators. The present study attends to this issue by exploring the types of evolutionary imagery deployed by secondary students. Our visual design analysis revealed that students resorted to two larger categories of images when visually communicating evolution: spatial metaphors (images that provided a spatio-temporal account of human evolution as a metaphorical "walk" across time and space) and symbolic representations ("icons of evolution" such as personal portraits of Charles Darwin that simply evoked evolutionary theory rather than metaphorically conveying its conceptual contents). It is argued that students need opportunities to collaboratively critique evolutionary imagery and to extend their visual perception of evolution beyond dominant images.
Tian, Ruijun; Jin, Jing; Taylor, Lorne; Larsen, Brett; Quaggin, Susan E; Pawson, Tony
2013-04-01
Gangliosides are ubiquitous components of cell membranes. Their interactions with bacterial toxins and membrane-associated proteins (e.g. receptor tyrosine kinases) have important roles in the regulation of multiple cellular functions. Currently, an effective approach for measuring ganglioside-protein interactions especially in a large-scale fashion is largely missing. To this end, we report a facile MS-based approach to explore gangliosides extracted from cells and measure their interactions with protein of interest globally. We optimized a two-step protocol for extracting total gangliosides from cells within 2 h. Easy-to-use magnetic beads conjugated with a protein of interest were used to capture interacting gangliosides. To measure ganglioside-protein interaction on a global scale, we applied a high-sensitive LC-MS system, containing hydrophilic interaction LC separation and multiple reaction monitoring-based MS for ganglioside detection. Sensitivity for ganglioside GM1 is below 100 pg, and the whole analysis can be done in 20 min with isocratic elution. To measure ganglioside interactions with soluble vascular endothelial growth factor receptor 1 (sFlt1), we extracted and readily detected 36 species of gangliosides from perivascular retinal pigment epithelium cells across eight different classes. Twenty-three ganglioside species have significant interactions with sFlt1 as compared with IgG control based on p value cutoff <0.05. These results show that the described method provides a rapid and high-sensitive approach for systematically measuring ganglioside-protein interactions. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Parvinen, Kalle; Brännström, Åke
2016-08-01
Species that compete for access to or use of sites, such as parasitic mites attaching to honey bees or apple maggots laying eggs in fruits, can potentially increase their fitness by carefully selecting sites at which they face little or no competition. Here, we systematically investigate the evolution of site-selection strategies among animals competing for discrete sites. By developing and analyzing a mechanistic and population-dynamical model of site selection in which searching individuals encounter sites sequentially and can choose to accept or continue to search based on how many conspecifics are already there, we give a complete characterization of the different site-selection strategies that can evolve. We find that evolution of site-selection stabilizes population dynamics, promotes even distribution of individuals among sites, and occasionally causes evolutionary suicide. We also discuss the broader implications of our findings and propose how they can be reconciled with an earlier study (Nonaka et al. in J Theor Biol 317:96-104, 2013) that reported selection toward ever higher levels of aggregation among sites as a consequence of site-selection.
NASA Astrophysics Data System (ADS)
Wu, Chaoxing; Li, Fushan; Chen, Wei; Veeramalai, Chandrasekar Perumal; Ooi, Poh Choon; Guo, Tailiang
2015-03-01
The direct observation of single crystal graphene growth and its shape evolution is of fundamental importance to the understanding of graphene growth physicochemical mechanisms and the achievement of wafer-scale single crystalline graphene. Here we demonstrate the controlled formation of single crystal graphene with varying shapes, and directly observe the shape evolution of single crystal graphene by developing a localized-heating and rapid-quenching chemical vapor deposition (CVD) system based on electromagnetic induction heating. Importantly, rational control of circular, hexagonal, and dendritic single crystalline graphene domains can be readily obtained for the first time by changing the growth condition. Systematic studies suggest that the graphene nucleation only occurs during the initial stage, while the domain density is independent of the growth temperatures due to the surface-limiting effect. In addition, the direct observation of graphene domain shape evolution is employed for the identification of competing growth mechanisms including diffusion-limited, attachment-limited, and detachment-limited processes. Our study not only provides a novel method for morphology-controlled graphene synthesis, but also offers fundamental insights into the kinetics of single crystal graphene growth.
Self-Organization: Complex Dynamical Systems in the Evolution of Speech
NASA Astrophysics Data System (ADS)
Oudeyer, Pierre-Yves
Human vocalization systems are characterized by complex structural properties. They are combinatorial, based on the systematic reuse of phonemes, and the set of repertoires in human languages is characterized by both strong statistical regularities—universals—and a great diversity. Besides, they are conventional codes culturally shared in each community of speakers. What are the origins of the forms of speech? What are the mechanisms that permitted their evolution in the course of phylogenesis and cultural evolution? How can a shared speech code be formed in a community of individuals? This chapter focuses on the way the concept of self-organization, and its interaction with natural selection, can throw light on these three questions. In particular, a computational model is presented which shows that a basic neural equipment for adaptive holistic vocal imitation, coupling directly motor and perceptual representations in the brain, can generate spontaneously shared combinatorial systems of vocalizations in a society of babbling individuals. Furthermore, we show how morphological and physiological innate constraints can interact with these self-organized mechanisms to account for both the formation of statistical regularities and diversity in vocalization systems.
Investigating yellow dung fly body size evolution in the field: Response to climate change?
Blanckenhorn, Wolf U
2015-08-01
Uncovering genetic responses to selection in wild populations typically requires tracking individuals over generations and use of animal models. Our group monitored the body size of one Swiss Yellow Dung Fly (Scathophaga stercoraria; Diptera: Scathophagidae) field population over 15 years, including intermittent common-garden rearing in the laboratory to assess body size with minimized environmental and maximized genetic variation. Contrary to expectations based on repeated heritability and phenotypic selection assessments over the years (reported elsewhere), field body sizes declined by >10% and common-garden laboratory sizes by >5% from 1993 to 2009. Our results confirm the temperature-size rule (smaller when warmer) and, albeit entirely correlational, could be mediated by climate change, as over this period mean temperature at the site increased by 0.5°C, although alternative systematic environmental changes cannot be entirely excluded. Monitoring genetic responses to selection in wild invertebrate populations is thus possible, though indirect, and wild populations may evolve in directions not consistent with strongly positive directional selection favoring large body size. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.
ERIC Educational Resources Information Center
Ziadie, M. A.; Andrews, T. C.
2018-01-01
Evolution is a unifying theory in biology and is challenging for undergraduates to learn. An instructor's ability to help students learn is influenced by pedagogical content knowledge (PCK), which is topic-specific knowledge of teaching and learning. Instructors need PCK for every topic they teach, which is a tremendous body of knowledge to…
The evolution of bacterial cell size: the internal diffusion-constraint hypothesis.
Gallet, Romain; Violle, Cyrille; Fromin, Nathalie; Jabbour-Zahab, Roula; Enquist, Brian J; Lenormand, Thomas
2017-07-01
Size is one of the most important biological traits influencing organismal ecology and evolution. However, we know little about the drivers of body size evolution in unicellulars. A long-term evolution experiment (Lenski's LTEE) in which Escherichia coli adapts to a simple glucose medium has shown that not only the growth rate and the fitness of the bacterium increase over time but also its cell size. This increase in size contradicts prominent 'external diffusion' theory (EDC) predicting that cell size should have evolved toward smaller cells. Among several scenarios, we propose and test an alternative 'internal diffusion-constraint' (IDC) hypothesis for cell size evolution. A change in cell volume affects metabolite concentrations in the cytoplasm. The IDC states that a higher metabolism can be achieved by a reduction in the molecular traffic time inside of the cell, by increasing its volume. To test this hypothesis, we studied a population from the LTEE. We show that bigger cells with greater growth and CO 2 production rates and lower mass-to-volume ratio were selected over time in the LTEE. These results are consistent with the IDC hypothesis. This novel hypothesis offers a promising approach for understanding the evolutionary constraints on cell size.
Evolution, biogeography, and systematics of Puriana: evolution and speciation in Ostracoda, III.
Cronin, T. M.
1987-01-01
Three types of geographic isolation - land barriers, deep water barriers, and climatic barriers - resulted in three distinct evolutionary responses in Neogene and Quaternary species of the epineritic ostracode genus Puriana. Through systematic, paleobiogeographic, and morphologic study of several hundred fossil and Recent populations from the eastern Pacific, western Atlantic, Gulf of Mexico, and the Caribbean, the phylogeny of the genus and the geography of speciation events were determined. Isolation of large populations by the Isthumus of Panama during the Pliocene did not lead to lineage splitting in species known to have existed before the Isthmus formed. Conversely, the establishment of small isolated populations on Caribbean islands by passive dispersal mechanisms frequently led to the evolution of new species or subspecies. Climatic changes along the southeastern United States during the Pliocene also catalyzed possible parapatric speciation as populations that immigrated to the northeastern periphery of the genus' range split to form new species. The results provide evidence that evolutionary models describing the influence of abiotic events on patterns of evolution and speciation can be tested using properly selected tectonic and climatic events and fossil groups amenable to species-level analysis. Two new species, P. bajaensis and P. paikensis, are described. -Author
Prebiological evolution and the metabolic origins of life.
Pratt, Andrew J
2011-01-01
The chemoton model of cells posits three subsystems: metabolism, compartmentalization, and information. A specific model for the prebiological evolution of a reproducing system with rudimentary versions of these three interdependent subsystems is presented. This is based on the initial emergence and reproduction of autocatalytic networks in hydrothermal microcompartments containing iron sulfide. The driving force for life was catalysis of the dissipation of the intrinsic redox gradient of the planet. The codependence of life on iron and phosphate provides chemical constraints on the ordering of prebiological evolution. The initial protometabolism was based on positive feedback loops associated with in situ carbon fixation in which the initial protometabolites modified the catalytic capacity and mobility of metal-based catalysts, especially iron-sulfur centers. A number of selection mechanisms, including catalytic efficiency and specificity, hydrolytic stability, and selective solubilization, are proposed as key determinants for autocatalytic reproduction exploited in protometabolic evolution. This evolutionary process led from autocatalytic networks within preexisting compartments to discrete, reproducing, mobile vesicular protocells with the capacity to use soluble sugar phosphates and hence the opportunity to develop nucleic acids. Fidelity of information transfer in the reproduction of these increasingly complex autocatalytic networks is a key selection pressure in prebiological evolution that eventually leads to the selection of nucleic acids as a digital information subsystem and hence the emergence of fully functional chemotons capable of Darwinian evolution.
Brauner, C J; Matey, V; Wilson, J M; Bernier, N J; Val, A L
2004-04-01
The transition from aquatic to aerial respiration is associated with dramatic physiological changes in relation to gas exchange, ion regulation, acid-base balance and nitrogenous waste excretion. Arapaima gigas is one of the most obligate extant air-breathing fishes, representing a remarkable model system to investigate (1) how the transition from aquatic to aerial respiration affects gill design and (2) the relocation of physiological processes from the gills to the kidney during the evolution of air-breathing. Arapaima gigas undergoes a transition from water- to air-breathing during development, resulting in striking changes in gill morphology. In small fish (10 g), the gills are qualitatively similar in appearance to another closely related water-breathing fish (Osteoglossum bicirrhosum); however, as fish grow (100-1000 g), the inter-lamellar spaces become filled with cells, including mitochondria-rich (MR) cells, leaving only column-shaped filaments. At this stage, there is a high density of MR cells and strong immunolocalization of Na(+)/K(+)-ATPase along the outer cell layer of the gill filament. Despite the greatly reduced overall gill surface area, which is typical of obligate air-breathing fish, the gills may remain an important site for ionoregulation and acid-base regulation. The kidney is greatly enlarged in A. gigas relative to that in O. bicirrhosum and may comprise a significant pathway for nitrogenous waste excretion. Quantification of the physiological role of the gill and the kidney in A. gigas during development and in adults will yield important insights into developmental physiology and the evolution of air-breathing.
Real-time evolution of a large-scale relativistic jet
NASA Astrophysics Data System (ADS)
Martí, Josep; Luque-Escamilla, Pedro L.; Romero, Gustavo E.; Sánchez-Sutil, Juan R.; Muñoz-Arjonilla, Álvaro J.
2015-06-01
Context. Astrophysical jets are ubiquitous in the Universe on all scales, but their large-scale dynamics and evolution in time are hard to observe since they usually develop at a very slow pace. Aims: We aim to obtain the first observational proof of the expected large-scale evolution and interaction with the environment in an astrophysical jet. Only jets from microquasars offer a chance to witness the real-time, full-jet evolution within a human lifetime, since they combine a "short", few parsec length with relativistic velocities. Methods: The methodology of this work is based on a systematic recalibraton of interferometric radio observations of microquasars available in public archives. In particular, radio observations of the microquasar GRS 1758-258 over less than two decades have provided the most striking results. Results: Significant morphological variations in the extended jet structure of GRS 1758-258 are reported here that were previously missed. Its northern radio lobe underwent a major morphological variation that rendered the hotspot undetectable in 2001 and reappeared again in the following years. The reported changes confirm the Galactic nature of the source. We tentatively interpret them in terms of the growth of instabilities in the jet flow. There is also evidence of surrounding cocoon. These results can provide a testbed for models accounting for the evolution of jets and their interaction with the environment.
Analysis of Pressure Variations in a Low-Pressure Nickel-Hydrogen Battery – Part 1
Purushothaman, B. K.; Wainright, J. S.
2012-01-01
A low pressure nickel-hydrogen battery using either a metal hydride or gaseous hydrogen for H2 storage has been developed for use in implantable neuroprosthetic devices. In this paper, pressure variations inside the cell for the gaseous hydrogen version are analyzed and correlated with oxygen evolution side reaction at the end of charging, the recombination of oxygen with hydrogen during charging and a subsequent rest period, and the self-discharge of the nickel electrode. About 70% of the recombination occurred simultaneously with oxygen evolution during charging and the remaining oxygen recombined with hydrogen during the 1st hour after charging. Self-discharge of the cell varies linearly with hydrogen pressure at a given state of charge and increased with increasing battery charge levels. The coulometric efficiency calculated based on analysis of the pressure-time data agreed well with the efficiency calculated based on the current-time data. Pressure variations in the battery are simulated accurately to predict coulometric efficiency and the state of charge of the cell, factors of extreme importance for a battery intended for implantation within the human body. PMID:22423175
Analysis of Pressure Variations in a Low-Pressure Nickel-Hydrogen Battery - Part 1.
Purushothaman, B K; Wainright, J S
2012-05-15
A low pressure nickel-hydrogen battery using either a metal hydride or gaseous hydrogen for H(2) storage has been developed for use in implantable neuroprosthetic devices. In this paper, pressure variations inside the cell for the gaseous hydrogen version are analyzed and correlated with oxygen evolution side reaction at the end of charging, the recombination of oxygen with hydrogen during charging and a subsequent rest period, and the self-discharge of the nickel electrode. About 70% of the recombination occurred simultaneously with oxygen evolution during charging and the remaining oxygen recombined with hydrogen during the 1(st) hour after charging. Self-discharge of the cell varies linearly with hydrogen pressure at a given state of charge and increased with increasing battery charge levels. The coulometric efficiency calculated based on analysis of the pressure-time data agreed well with the efficiency calculated based on the current-time data. Pressure variations in the battery are simulated accurately to predict coulometric efficiency and the state of charge of the cell, factors of extreme importance for a battery intended for implantation within the human body.
Raman scattering in the RTiO3 family of Mott-Hubbard insulators
NASA Astrophysics Data System (ADS)
Reedyk, M.; Crandles, D. A.; Cardona, M.; Garrett, J. D.; Greedan, J. E.
1997-01-01
Raman-scattering measurements have been carried out for crystals of the RTiO3 (R=La,Ce,Pr,Nd,Sm,Gd) system whose members are Mott-Hubbard insulators. RTiO3 has an orthorhombically distorted perovskite unit cell. The distortion increases systematically from LaTiO3 to GdTiO3 and is accompanied by changes in electronic structure (decreasing W/U ratio). As a consequence of the changing electronic properties, the Raman spectrum shows an interesting evolution of both the phonon features and the electronic continuum. Most notable are (1) a redistribution in the spectral shape of the electronic background, (2) a systematic change in line shape, and a dramatic increase in the center frequency of one of the phonon modes from 287 cm-1 in LaTiO3 to 385 cm-1 in GdTiO3, and (3) the observation of resonance effects in the most insulating members of the series. The appearance of a free-carrier component in the electronic-scattering background, which seems to be related to systematic self-energy effects of the phonon near 300 cm-1, is unexpected. It is likely the result of increased doping due to a greater facility for rare-earth vacancies to form in large R3+ ionic radius members of the series. A systematic increase in the continuum scattering rate is also observed and indicates that the free carriers are not scattering off rare-earth vacancies but rather that the scattering mechanism originates from changes in electronic structure.
Cassin, Andrew M.; Soltis, Douglas E.; Miles, Nicholas W.; Melkonian, Michael; Melkonian, Barbara; Wu, Shuangxiu; Edger, Patrick P.; Carpenter, Eric J.
2017-01-01
The carbohydrate-rich cell walls of land plants and algae have been the focus of much interest given the value of cell wall-based products to our current and future economies. Hydroxyproline-rich glycoproteins (HRGPs), a major group of wall glycoproteins, play important roles in plant growth and development, yet little is known about how they have evolved in parallel with the polysaccharide components of walls. We investigate the origins and evolution of the HRGP superfamily, which is commonly divided into three major multigene families: the arabinogalactan proteins (AGPs), extensins (EXTs), and proline-rich proteins. Using motif and amino acid bias, a newly developed bioinformatics pipeline, we identified HRGPs in sequences from the 1000 Plants transcriptome project (www.onekp.com). Our analyses provide new insights into the evolution of HRGPs across major evolutionary milestones, including the transition to land and the early radiation of angiosperms. Significantly, data mining reveals the origin of glycosylphosphatidylinositol (GPI)-anchored AGPs in green algae and a 3- to 4-fold increase in GPI-AGPs in liverworts and mosses. The first detection of cross-linking (CL)-EXTs is observed in bryophytes, which suggests that CL-EXTs arose though the juxtaposition of preexisting SPn EXT glycomotifs with refined Y-based motifs. We also detected the loss of CL-EXT in a few lineages, including the grass family (Poaceae), that have a cell wall composition distinct from other monocots and eudicots. A key challenge in HRGP research is tracking individual HRGPs throughout evolution. Using the 1000 Plants output, we were able to find putative orthologs of Arabidopsis pollen-specific GPI-AGPs in basal eudicots. PMID:28446636
Insights into the Evolution of Hydroxyproline-Rich Glycoproteins from 1000 Plant Transcriptomes.
Johnson, Kim L; Cassin, Andrew M; Lonsdale, Andrew; Wong, Gane Ka-Shu; Soltis, Douglas E; Miles, Nicholas W; Melkonian, Michael; Melkonian, Barbara; Deyholos, Michael K; Leebens-Mack, James; Rothfels, Carl J; Stevenson, Dennis W; Graham, Sean W; Wang, Xumin; Wu, Shuangxiu; Pires, J Chris; Edger, Patrick P; Carpenter, Eric J; Bacic, Antony; Doblin, Monika S; Schultz, Carolyn J
2017-06-01
The carbohydrate-rich cell walls of land plants and algae have been the focus of much interest given the value of cell wall-based products to our current and future economies. Hydroxyproline-rich glycoproteins (HRGPs), a major group of wall glycoproteins, play important roles in plant growth and development, yet little is known about how they have evolved in parallel with the polysaccharide components of walls. We investigate the origins and evolution of the HRGP superfamily, which is commonly divided into three major multigene families: the arabinogalactan proteins (AGPs), extensins (EXTs), and proline-rich proteins. Using motif and amino acid bias, a newly developed bioinformatics pipeline, we identified HRGPs in sequences from the 1000 Plants transcriptome project (www.onekp.com). Our analyses provide new insights into the evolution of HRGPs across major evolutionary milestones, including the transition to land and the early radiation of angiosperms. Significantly, data mining reveals the origin of glycosylphosphatidylinositol (GPI)-anchored AGPs in green algae and a 3- to 4-fold increase in GPI-AGPs in liverworts and mosses. The first detection of cross-linking (CL)-EXTs is observed in bryophytes, which suggests that CL-EXTs arose though the juxtaposition of preexisting SP n EXT glycomotifs with refined Y-based motifs. We also detected the loss of CL-EXT in a few lineages, including the grass family (Poaceae), that have a cell wall composition distinct from other monocots and eudicots. A key challenge in HRGP research is tracking individual HRGPs throughout evolution. Using the 1000 Plants output, we were able to find putative orthologs of Arabidopsis pollen-specific GPI-AGPs in basal eudicots. © 2017 American Society of Plant Biologists. All Rights Reserved.
NASA Astrophysics Data System (ADS)
Banerji, Manda; Ferreras, Ignacio; Abdalla, Filipe B.; Hewett, Paul; Lahav, Ofer
2010-03-01
We present an analysis of the evolution of 8625 luminous red galaxies (LRGs) between z = 0.4 and 0.8 in the 2dF and Sloan Digital Sky Survey LRG and QSO (2SLAQ) survey. The LRGs are split into redshift bins and the evolution of both the luminosity and stellar mass function with redshift is considered and compared to the assumptions of a passive evolution scenario. We draw attention to several sources of systematic error that could bias the evolutionary predictions made in this paper. While the inferred evolution is found to be relatively unaffected by the exact choice of spectral evolution model used to compute K + e corrections, we conclude that photometric errors could be a source of significant bias in colour-selected samples such as this, in particular when using parametric maximum likelihood based estimators. We find that the evolution of the most massive LRGs is consistent with the assumptions of passive evolution and that the stellar mass assembly of the LRGs is largely complete by z ~ 0.8. Our findings suggest that massive galaxies with stellar masses above 1011Msolar must have undergone merging and star formation processes at a very early stage (z >~ 1). This supports the emerging picture of downsizing in both the star formation as well as the mass assembly of early-type galaxies. Given that our spectroscopic sample covers an unprecedentedly large volume and probes the most massive end of the galaxy mass function, we find that these observational results present a significant challenge for many current models of galaxy formation.
2015-01-01
Bioorthogonal reactions, including the strain-promoted azide–alkyne cycloaddition (SPAAC) and inverse electron demand Diels–Alder (iEDDA) reactions, have become increasingly popular for live-cell imaging applications. However, the stability and reactivity of reagents has never been systematically explored in the context of a living cell. Here we report a universal, organelle-targetable system based on HaloTag protein technology for directly comparing bioorthogonal reagent reactivity, specificity, and stability using clickable HaloTag ligands in various subcellular compartments. This system enabled a detailed comparison of the bioorthogonal reactions in live cells and informed the selection of optimal reagents and conditions for live-cell imaging studies. We found that the reaction of sTCO with monosubstituted tetrazines is the fastest reaction in cells; however, both reagents have stability issues. To address this, we introduced a new variant of sTCO, Ag-sTCO, which has much improved stability and can be used directly in cells for rapid bioorthogonal reactions with tetrazines. Utilization of Ag complexes of conformationally strained trans-cyclooctenes should greatly expand their usefulness especially when paired with less reactive, more stable tetrazines. PMID:26270632
Murrey, Heather E; Judkins, Joshua C; Am Ende, Christopher W; Ballard, T Eric; Fang, Yinzhi; Riccardi, Keith; Di, Li; Guilmette, Edward R; Schwartz, Joel W; Fox, Joseph M; Johnson, Douglas S
2015-09-09
Bioorthogonal reactions, including the strain-promoted azide-alkyne cycloaddition (SPAAC) and inverse electron demand Diels-Alder (iEDDA) reactions, have become increasingly popular for live-cell imaging applications. However, the stability and reactivity of reagents has never been systematically explored in the context of a living cell. Here we report a universal, organelle-targetable system based on HaloTag protein technology for directly comparing bioorthogonal reagent reactivity, specificity, and stability using clickable HaloTag ligands in various subcellular compartments. This system enabled a detailed comparison of the bioorthogonal reactions in live cells and informed the selection of optimal reagents and conditions for live-cell imaging studies. We found that the reaction of sTCO with monosubstituted tetrazines is the fastest reaction in cells; however, both reagents have stability issues. To address this, we introduced a new variant of sTCO, Ag-sTCO, which has much improved stability and can be used directly in cells for rapid bioorthogonal reactions with tetrazines. Utilization of Ag complexes of conformationally strained trans-cyclooctenes should greatly expand their usefulness especially when paired with less reactive, more stable tetrazines.
Crunteanu, Aurelian; Givernaud, Julien; Leroy, Jonathan; Mardivirin, David; Champeaux, Corinne; Orlianges, Jean-Christophe; Catherinot, Alain; Blondy, Pierre
2010-12-01
Vanadium dioxide is an intensively studied material that undergoes a temperature-induced metal-insulator phase transition accompanied by a large change in electrical resistivity. Electrical switches based on this material show promising properties in terms of speed and broadband operation. The exploration of the failure behavior and reliability of such devices is very important in view of their integration in practical electronic circuits. We performed systematic lifetime investigations of two-terminal switches based on the electrical activation of the metal-insulator transition in VO 2 thin films. The devices were integrated in coplanar microwave waveguides (CPWs) in series configuration. We detected the evolution of a 10 GHz microwave signal transmitted through the CPW, modulated by the activation of the VO 2 switches in both voltage- and current-controlled modes. We demonstrated enhanced lifetime operation of current-controlled VO 2 -based switching (more than 260 million cycles without failure) compared with the voltage-activated mode (breakdown at around 16 million activation cycles). The evolution of the electrical self-oscillations of a VO 2 -based switch induced in the current-operated mode is a subtle indicator of the material properties modification and can be used to monitor its behavior under various external stresses in sensor applications.
Zinc oxide nanostructures as low-cost templates for neuronal circuit
NASA Astrophysics Data System (ADS)
Kritharidou, A.; Georgoussi, Z.; Tsamis, C.; Makarona, E.
2013-05-01
ZnO nanostructures were explored as templates for the development of topography-mediated neuronal cultures. Nanostructures of varying features were produced on 4" Si substrates via a rapid, facile and low-cost technique that allows the systematic investigation of nanotopographically-mediated formation of neuronal cultures. The developed ZnO-nanowire based templates were seeded with Neuro-2A mouse neuroblastoma cells and their viability over the course of 1 to 4 days was assessed. Our studies demonstrate that the ZnO-templates can support neuronal cell growth and proliferation suggesting that ZnO substrate can be used for the development of neuronal cell-based platform technologies.
Algorithm for cellular reprogramming.
Ronquist, Scott; Patterson, Geoff; Muir, Lindsey A; Lindsly, Stephen; Chen, Haiming; Brown, Markus; Wicha, Max S; Bloch, Anthony; Brockett, Roger; Rajapakse, Indika
2017-11-07
The day we understand the time evolution of subcellular events at a level of detail comparable to physical systems governed by Newton's laws of motion seems far away. Even so, quantitative approaches to cellular dynamics add to our understanding of cell biology. With data-guided frameworks we can develop better predictions about, and methods for, control over specific biological processes and system-wide cell behavior. Here we describe an approach for optimizing the use of transcription factors (TFs) in cellular reprogramming, based on a device commonly used in optimal control. We construct an approximate model for the natural evolution of a cell-cycle-synchronized population of human fibroblasts, based on data obtained by sampling the expression of 22,083 genes at several time points during the cell cycle. To arrive at a model of moderate complexity, we cluster gene expression based on division of the genome into topologically associating domains (TADs) and then model the dynamics of TAD expression levels. Based on this dynamical model and additional data, such as known TF binding sites and activity, we develop a methodology for identifying the top TF candidates for a specific cellular reprogramming task. Our data-guided methodology identifies a number of TFs previously validated for reprogramming and/or natural differentiation and predicts some potentially useful combinations of TFs. Our findings highlight the immense potential of dynamical models, mathematics, and data-guided methodologies for improving strategies for control over biological processes. Copyright © 2017 the Author(s). Published by PNAS.
Communicating the molecular basis of cancer cell-by-cell: an interview with Tatsushi Igaki.
Igaki, Tatsushi
2015-12-01
Tatsushi Igaki is currently based at the Kyoto University Graduate School of Biostudies, where he leads a research group dedicated to using Drosophila genetics to build a picture of the cell-cell communications underlying the establishment and maintenance of multicellular systems. His work has provided insight into the molecular bases of cell competition in the context of development and tumorigenesis, including the landmark discovery that oncogenic cells communicate with normal cells in the tumor microenvironment to induce tumor progression in a non-autonomous fashion. In this interview, he describes his career path, highlighting the shift in his research focus from the basic principles of apoptosis to clonal evolution in cancer, and also explains why Drosophila provides a powerful model system for studying cancer biology. © 2015. Published by The Company of Biologists Ltd.
Origin and thermal evolution of Mars
NASA Technical Reports Server (NTRS)
Schubert, G.; Solomon, Sean C.; Turcotte, D. L.; Drake, M. J.; Sleep, N. H.
1993-01-01
The thermal evolution of Mars is governed by subsolidus mantle convection beneath a thick lithosphere. Models of the interior evolution are developed by parameterizing mantle convective heat transport in terms of mantle viscosity, the superadiabatic temperature rise across the mantle and mantle heat production. Geological, geophysical, and geochemical observations of the composition and structure of the interior and of the timing of major events in Martian evolution, such as global differentiation, atmospheric outgassing and the formation of the hemispherical dichotomy and Tharsis, are used to constrain the model computations. Isotope systematics of SNC meteorites suggest core formation essentially contemporaneously with the completion of accretion. Other aspects of this investigation are discussed.
The generalized DMPK equation revisited: towards a systematic derivation
NASA Astrophysics Data System (ADS)
Douglas, Andrew; Markoš, Peter; Muttalib, K. A.
2014-03-01
The generalized Dorokov-Mello-Pereyra-Kumar (DMPK) equation has recently been used to obtain a family of very broad and highly asymmetric conductance distributions for three-dimensional disordered conductors. However, there are two major criticisms of the derivation of the generalized DMPK equation: (1) certain eigenvector correlations were neglected based on qualitative arguments that cannot be valid for all strengths of disorder, and (2) the repulsion between two closely spaced eigenvalues were not rigorously governed by symmetry considerations. In this work we show that it is possible to address both criticisms by including the eigenvalue and eigenvector correlations in a systematic and controlled way. It turns out that the added correlations determine the evolution of the Jacobian, without affecting the evaluation of the conductance distributions. They also guarantee the symmetry requirements. In addition, we obtain an exact relationship between the eigenvectors and the Lyapunov exponents leading to a sum rule for the latter at all disorder strengths.
The bankfull hydraulic geometry of evolving meander bends
NASA Astrophysics Data System (ADS)
Monegaglia, F.; Tubino, M.; Zolezzi, G.
2017-12-01
Changes in the bankfull hydraulic geometry of meandering rivers associated with meander growth from incipient meandering to cutoffs have seldom been analysed in detail. Such information is also needed by meander morphodynamic models, most of which simulate the evolution of bankfull channel geometry by simply accounting for channel slope reduction inversely proportional to elongation, while changes in bankfull channel width are often neglected or, when they are considered, they are not consistent with the few available observations. To address these gaps we first perform an extensive, systematic, bend-scale evolutionary analysis of bankfull channel widths in several large meandering rivers in the Amazon basin, over a three decades time period, from remotely sensed field data. The analysis consistently show a slight decreasing trend of the bankfull channel width during the planform evolution towards cutoff. Furthermore, we develop a physically based model for the evolution of bankfull channel geometry during the planform development of meandering rivers. The model is based on the conservation of sediment discharge. An integrated one-dimensional Exner equation that accounts for meander elongation, sediment supply conservation and sediment income from the channel banks, allows us to predict the evolution of the channel slope. The evolution of the channel width is modeled through a threshold equation. The model correctly predicts the slight variability of channel width during meander development and a gentler reduction of the channel slope, which is mitigated by the conservation of sediment supply. The bankfull geometry of highly dynamic meandering rivers is predicted to be elongation-dominated, while the one related to slowly evolving meandering rivers is sediment supply-dominated. Finally, we discuss the implications of the proposed modeling framework in terms of planform structure, meander shape and morphodynamic influence.
Neutralization of Staphylococcal Enterotoxin B by an Aptamer Antagonist
Wang, Kaiyu; Gan, Longjie; Jiang, Li; Zhang, Xianhui; Yang, Xiangyue; Chen, Min
2015-01-01
Staphylococcal enterotoxin B (SEB) is a major virulence factor for staphylococcal toxic shock syndrome (TSS). SEB activates a large subset of the T lymphocytic population, releasing proinflammatory cytokines. Blocking SEB-initiated toxicity may be an effective strategy for treating TSS. Using a process known as systematic evolution of ligands by exponential enrichment (SELEX), we identified an aptamer that can antagonize SEB with nanomolar binding affinity (Kd = 64 nM). The aptamer antagonist effectively inhibits SEB-mediated proliferation and cytokine secretion in human peripheral blood mononuclear cells. Moreover, a PEGylated aptamer antagonist significantly reduced mortality in a “double-hit” mouse model of SEB-induced TSS, established via sensitization with d-galactosamine followed by SEB challenge. Therefore, our novel aptamer antagonist may offer potential therapeutic efficacy against SEB-mediated TSS. PMID:25624325
Lada, Artem G.; Stepchenkova, Elena I.; Waisertreiger, Irina S. R.; Noskov, Vladimir N.; Dhar, Alok; Eudy, James D.; Boissy, Robert J.; Hirano, Masayuki; Rogozin, Igor B.; Pavlov, Youri I.
2013-01-01
Genetic information should be accurately transmitted from cell to cell; conversely, the adaptation in evolution and disease is fueled by mutations. In the case of cancer development, multiple genetic changes happen in somatic diploid cells. Most classic studies of the molecular mechanisms of mutagenesis have been performed in haploids. We demonstrate that the parameters of the mutation process are different in diploid cell populations. The genomes of drug-resistant mutants induced in yeast diploids by base analog 6-hydroxylaminopurine (HAP) or AID/APOBEC cytosine deaminase PmCDA1 from lamprey carried a stunning load of thousands of unselected mutations. Haploid mutants contained almost an order of magnitude fewer mutations. To explain this, we propose that the distribution of induced mutation rates in the cell population is uneven. The mutants in diploids with coincidental mutations in the two copies of the reporter gene arise from a fraction of cells that are transiently hypersensitive to the mutagenic action of a given mutagen. The progeny of such cells were never recovered in haploids due to the lethality caused by the inactivation of single-copy essential genes in cells with too many induced mutations. In diploid cells, the progeny of hypersensitive cells survived, but their genomes were saturated by heterozygous mutations. The reason for the hypermutability of cells could be transient faults of the mutation prevention pathways, like sanitization of nucleotide pools for HAP or an elevated expression of the PmCDA1 gene or the temporary inability of the destruction of the deaminase. The hypothesis on spikes of mutability may explain the sudden acquisition of multiple mutational changes during evolution and carcinogenesis. PMID:24039593
NASA Technical Reports Server (NTRS)
Beck, M.
1979-01-01
In approaching the extremely involved and complex problem of the origin of life, consideration of the coordination chemistry appeared not only as a possibility but as a necessity. The first model experiments appear to be promising because of prebiotic-type synthesis by means of transition-metal complexes. It is especially significant that in some instances various types of vitally important substances (nucleic bases, amino acids) are formed simultaneously. There is ground to hope that systematic studies in this field will clarify the role of transition-metal complexes in the organizatorial phase of chemical evolution. It is obvious that researchers working in the fields of the chemistry of cyano and carbonyl complexes, and of the catalytic effect of transition-metal complexes are best suited to study these aspects of the attractive and interesting problem of the origin of life.
Evolution of the Valley Position in Bulk Transition-Metal Chalcogenides and Their Monolayer Limit.
Yuan, Hongtao; Liu, Zhongkai; Xu, Gang; Zhou, Bo; Wu, Sanfeng; Dumcenco, Dumitru; Yan, Kai; Zhang, Yi; Mo, Sung-Kwan; Dudin, Pavel; Kandyba, Victor; Yablonskikh, Mikhail; Barinov, Alexei; Shen, Zhixun; Zhang, Shoucheng; Huang, Yingsheng; Xu, Xiaodong; Hussain, Zahid; Hwang, Harold Y; Cui, Yi; Chen, Yulin
2016-08-10
Layered transition metal chalcogenides with large spin orbit coupling have recently sparked much interest due to their potential applications for electronic, optoelectronic, spintronics, and valleytronics. However, most current understanding of the electronic structure near band valleys in momentum space is based on either theoretical investigations or optical measurements, leaving the detailed band structure elusive. For example, the exact position of the conduction band valley of bulk MoS2 remains controversial. Here, using angle-resolved photoemission spectroscopy with submicron spatial resolution (micro-ARPES), we systematically imaged the conduction/valence band structure evolution across representative chalcogenides MoS2, WS2, and WSe2, as well as the thickness dependent electronic structure from bulk to the monolayer limit. These results establish a solid basis to understand the underlying valley physics of these materials, and also provide a link between chalcogenide electronic band structure and their physical properties for potential valleytronics applications.
Fixation of slightly beneficial mutations: effects of life history.
Vindenes, Yngvild; Lee, Aline Magdalena; Engen, Steinar; Saether, Bernt-Erik
2010-04-01
Recent studies of rates of evolution have revealed large systematic differences among organisms with different life histories, both within and among taxa. Here, we consider how life history may affect the rate of evolution via its influence on the fixation probability of slightly beneficial mutations. Our approach is based on diffusion modeling for a finite, stage-structured population with stochastic population dynamics. The results, which are verified by computer simulations, demonstrate that even with complex population structure just two demographic parameters are sufficient to give an accurate approximation of the fixation probability of a slightly beneficial mutation. These are the reproductive value of the stage in which the mutation first occurs and the demographic variance of the population. The demographic variance also determines what influence population size has on the fixation probability. This model represents a substantial generalization of earlier models, covering a large range of life histories.
Tavazzi, Luigi
2016-03-01
The growing scientific knowledge and technology development are leading to radical changes in biological and medical research. The prevalent lines of development deal with a pragmatic evolution of controlled clinical trials, a massive diffusion of observational research, which is progressively incorporated in clinical practice, new models and designs of clinical research, the systematic use of information technology to build up vast networks of medical centers producing huge amounts of shared data to be managed through the big data methodology, personalized as well as precision medicine, a reshaped physician-patient relationship based on a co-working principle. All this is leading to profound changes in public health governance, a renewal of clinical epidemiology and prevention, a modified structure of several specific sectors of medical care, hopefully guided by scientific evidences. A few aspects of such an evolving picture are discussed in this article.
NASA Astrophysics Data System (ADS)
Zhuo, Zhao; Cai, Shi-Min; Tang, Ming; Lai, Ying-Cheng
2018-04-01
One of the most challenging problems in network science is to accurately detect communities at distinct hierarchical scales. Most existing methods are based on structural analysis and manipulation, which are NP-hard. We articulate an alternative, dynamical evolution-based approach to the problem. The basic principle is to computationally implement a nonlinear dynamical process on all nodes in the network with a general coupling scheme, creating a networked dynamical system. Under a proper system setting and with an adjustable control parameter, the community structure of the network would "come out" or emerge naturally from the dynamical evolution of the system. As the control parameter is systematically varied, the community hierarchies at different scales can be revealed. As a concrete example of this general principle, we exploit clustered synchronization as a dynamical mechanism through which the hierarchical community structure can be uncovered. In particular, for quite arbitrary choices of the nonlinear nodal dynamics and coupling scheme, decreasing the coupling parameter from the global synchronization regime, in which the dynamical states of all nodes are perfectly synchronized, can lead to a weaker type of synchronization organized as clusters. We demonstrate the existence of optimal choices of the coupling parameter for which the synchronization clusters encode accurate information about the hierarchical community structure of the network. We test and validate our method using a standard class of benchmark modular networks with two distinct hierarchies of communities and a number of empirical networks arising from the real world. Our method is computationally extremely efficient, eliminating completely the NP-hard difficulty associated with previous methods. The basic principle of exploiting dynamical evolution to uncover hidden community organizations at different scales represents a "game-change" type of approach to addressing the problem of community detection in complex networks.
Morphology evolution in high-performance polymer solar cells processed from nonhalogenated solvent
Cai, Wanzhu; Liu, Peng; Jin, Yaocheng; ...
2015-05-26
A new processing protocol based on non-halogenated solvent and additive is developed to produce polymer solar cells with power conversion efficiencies better than those processed from commonly used halogenated solvent-additive pair. Morphology studies show that good performance correlates with a finely distributed nanomorphology with a well-defined polymer fibril network structure, which leads to balanced charge transport in device operation.
Harris, Joshua D; Brand, Jefferson C; Cote, Mark P; Dhawan, Aman
2017-08-01
Within the health care environment, there has been a recent and appropriate trend towards emphasizing the value of care provision. Reduced cost and higher quality improve the value of care. Quality is a challenging, heterogeneous, variably defined concept. At the core of quality is the patient's outcome, quantified by a vast assortment of subjective and objective outcome measures. There has been a recent evolution towards evidence-based medicine in health care, clearly elucidating the role of high-quality evidence across groups of patients and studies. Synthetic studies, such as systematic reviews and meta-analyses, are at the top of the evidence-based medicine hierarchy. Thus, these investigations may be the best potential source of guiding diagnostic, therapeutic, prognostic, and economic medical decision making. Systematic reviews critically appraise and synthesize the best available evidence to provide a conclusion statement (a "take-home point") in response to a specific answerable clinical question. A meta-analysis uses statistical methods to quantitatively combine data from single studies. Meta-analyses should be performed with high methodological quality homogenous studies (Level I or II) or evidence randomized studies, to minimize confounding variable bias. When it is known that the literature is inadequate or a recent systematic review has already been performed with a demonstration of insufficient data, then a new systematic review does not add anything meaningful to the literature. PROSPERO registration and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines assist authors in the design and conduct of systematic reviews and should always be used. Complete transparency of the conduct of the review permits reproducibility and improves fidelity of the conclusions. Pooling of data from overly dissimilar investigations should be avoided. This particularly applies to Level IV evidence, that is, noncomparative investigations. With proper technique, systematic reviews and meta-analyses have the potential to be powerful investigations that efficiently assist clinicians in decision making. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.
Ng, David; Pauli, Jutta; Resch-Genger, Ute; Kühn, Enrico; Heuer, Steffen; Beisker, Wolfgang; Köster, Reinhard W.; Zitzelsberger, Horst; Caldwell, Randolph B
2014-01-01
With rare exceptions, natural evolution is an extremely slow process. One particularly striking exception in the case of protein evolution is in the natural production of antibodies. Developing B cells activate and diversify their immunoglobulin (Ig) genes by recombination, gene conversion (GC) and somatic hypermutation (SHM). Iterative cycles of hypermutation and selection continue until antibodies of high antigen binding specificity emerge (affinity maturation). The avian B cell line DT40, a cell line which is highly amenable to genetic manipulation and exhibits a high rate of targeted integration, utilizes both GC and SHM. Targeting the DT40's diversification machinery onto transgenes of interest inserted into the Ig loci and coupling selective pressure based on the desired outcome mimics evolution. Here we further demonstrate the usefulness of this platform technology by selectively pressuring a large shift in the spectral properties of the fluorescent protein eqFP615 into the highly stable and advanced optical imaging expediting fluorescent protein Amrose. The method is advantageous as it is time and cost effective and no prior knowledge of the outcome protein's structure is necessary. Amrose was evolved to have high excitation at 633 nm and excitation/emission into the far-red, which is optimal for whole-body and deep tissue imaging as we demonstrate in the zebrafish and mouse model. PMID:25192257
Schoetz, Ulrike; Deliolanis, Nikolaos C; Ng, David; Pauli, Jutta; Resch-Genger, Ute; Kühn, Enrico; Heuer, Steffen; Beisker, Wolfgang; Köster, Reinhard W; Zitzelsberger, Horst; Caldwell, Randolph B
2014-01-01
With rare exceptions, natural evolution is an extremely slow process. One particularly striking exception in the case of protein evolution is in the natural production of antibodies. Developing B cells activate and diversify their immunoglobulin (Ig) genes by recombination, gene conversion (GC) and somatic hypermutation (SHM). Iterative cycles of hypermutation and selection continue until antibodies of high antigen binding specificity emerge (affinity maturation). The avian B cell line DT40, a cell line which is highly amenable to genetic manipulation and exhibits a high rate of targeted integration, utilizes both GC and SHM. Targeting the DT40's diversification machinery onto transgenes of interest inserted into the Ig loci and coupling selective pressure based on the desired outcome mimics evolution. Here we further demonstrate the usefulness of this platform technology by selectively pressuring a large shift in the spectral properties of the fluorescent protein eqFP615 into the highly stable and advanced optical imaging expediting fluorescent protein Amrose. The method is advantageous as it is time and cost effective and no prior knowledge of the outcome protein's structure is necessary. Amrose was evolved to have high excitation at 633 nm and excitation/emission into the far-red, which is optimal for whole-body and deep tissue imaging as we demonstrate in the zebrafish and mouse model.
Guo, Zhen; Li, Ying; Guo, Haiyan
2017-12-01
To improve the photoproduction of hydrogen (H 2 ) by a green algae-based system, the effect of light/dark regimens on H 2 photoproduction regulated by carbonyl cyanide m-chlorophenylhydrazone (CCCP) was investigated. A fuel cell was integrated into a photobioreactor to allow online monitoring of the H 2 evolution rate and decrease potential H 2 feedback inhibition by consuming the generated H 2 in situ. During the first 15 h of H 2 evolution, the system was subjected to dark treatment after initial light illumination (L/D = 6/9 h, 9/6 h, and 12/3 h). After the dark period, all systems were again exposed to light illumination until H 2 evolution stopped. Two peaks were observed in the H 2 evolution rate under all three light/dark regimens. Additionally, a high H 2 yield of 126 ± 10 mL L -1 was achieved using a light/dark regimen of L 9 h/D 6 h/L until H 2 production ceased, which was 1.6 times higher than that obtained under continuous illumination. H 2 production was accompanied by some physiological and morphological changes in the cells. The results indicated that light/dark regimens improved the duration and yield of H 2 photoproduction by the CCCP-regulated process of Tetraselmis subcordiformis.
Ren, Juan; Yu, Shiyan; Gao, Nan; Zou, Qingze
2013-11-01
In this paper, a control-based approach to replace the conventional method to achieve accurate indentation quantification is proposed for nanomechanical measurement of live cells using atomic force microscope. Accurate indentation quantification is central to probe-based nanomechanical property measurement. The conventional method for in-liquid nanomechanical measurement of live cells, however, fails to accurately quantify the indentation as effects of the relative probe acceleration and the hydrodynamic force are not addressed. As a result, significant errors and uncertainties are induced in the nanomechanical properties measured. In this paper, a control-based approach is proposed to account for these adverse effects by tracking the same excitation force profile on both a live cell and a hard reference sample through the use of an advanced control technique, and by quantifying the indentation from the difference of the cantilever base displacement in these two measurements. The proposed control-based approach not only eliminates the relative probe acceleration effect with no need to calibrate the parameters involved, but it also reduces the hydrodynamic force effect significantly when the force load rate becomes high. We further hypothesize that, by using the proposed control-based approach, the rate-dependent elastic modulus of live human epithelial cells under different stress conditions can be reliably quantified to predict the elasticity evolution of cell membranes, and hence can be used to predict cellular behaviors. By implementing the proposed approach, the elastic modulus of HeLa cells before and after the stress process were quantified as the force load rate was changed over three orders of magnitude from 0.1 to 100 Hz, where the amplitude of the applied force and the indentation were at 0.4-2 nN and 250-450 nm, respectively. The measured elastic modulus of HeLa cells showed a clear power-law dependence on the load rate, both before and after the stress process. Moreover, the elastic modulus of HeLa cells was substantially reduced by two to five times due to the stress process. Thus, our measurements demonstrate that the control-based protocol is effective in quantifying and characterizing the evolution of nanomechanical properties during the stress process of live cells.
Blood-Based Analyses of Cancer: Circulating Tumor Cells and Circulating Tumor DNA
Haber, Daniel A.; Velculescu, Victor E.
2015-01-01
The ability to study nonhematologic cancers through noninvasive sampling of blood is one of the most exciting and rapidly advancing fields in cancer diagnostics. This has been driven both by major technologic advances, including the isolation of intact cancer cells and the analysis of cancer cell–derived DNA from blood samples, and by the increasing application of molecularly driven therapeutics, which rely on such accurate and timely measurements of critical biomarkers. Moreover, the dramatic efficacy of these potent cancer therapies drives the selection for additional genetic changes as tumors acquire drug resistance, necessitating repeated sampling of cancer cells to adjust therapy in response to tumor evolution. Together, these advanced noninvasive diagnostic capabilities and their applications in guiding precision cancer therapies are poised to change the ways in which we select and monitor cancer treatments. Significance Recent advances in technologies to analyze circulating tumor cells and circulating tumor DNA are setting the stage for real-time, noninvasive monitoring of cancer and providing novel insights into cancer evolution, invasion, and metastasis. PMID:24801577
Iridium-Based Nanowires as Highly Active, Oxygen Evolution Reaction Electrocatalysts
DOE Office of Scientific and Technical Information (OSTI.GOV)
Alia, Shaun M.; Shulda, Sarah; Ngo, Chilan
Iridium-nickel (Ir-Ni) and iridium-cobalt (Ir-Co) nanowires have been synthesized by galvanic displacement and studied for their potential to increase the performance and durability of electrolysis systems. Performances of Ir-Ni and Ir-Co nanowires for the oxygen evolution reaction (OER) have been measured in rotating disk electrode half-cells and single-cell electrolyzers and compared with commercial baselines and literature references. The nanowire catalysts showed improved mass activity, by more than an order of magnitude compared with commercial Ir nanoparticles in half-cell tests. The nanowire catalysts also showed greatly improved durability, when acid-leached to remove excess Ni and Co. Both Ni and Co templatesmore » were found to have similarly positive impacts, although specific differences between the two systems are revealed. In single-cell electrolysis testing, nanowires exceeded the performance of Ir nanoparticles by 4-5 times, suggesting that significant reductions in catalyst loading are possible without compromising performance.« less
Iridium-Based Nanowires as Highly Active, Oxygen Evolution Reaction Electrocatalysts
Alia, Shaun M.; Shulda, Sarah; Ngo, Chilan; ...
2018-01-22
Iridium-nickel (Ir-Ni) and iridium-cobalt (Ir-Co) nanowires have been synthesized by galvanic displacement and studied for their potential to increase the performance and durability of electrolysis systems. Performances of Ir-Ni and Ir-Co nanowires for the oxygen evolution reaction (OER) have been measured in rotating disk electrode half-cells and single-cell electrolyzers and compared with commercial baselines and literature references. The nanowire catalysts showed improved mass activity, by more than an order of magnitude compared with commercial Ir nanoparticles in half-cell tests. The nanowire catalysts also showed greatly improved durability, when acid-leached to remove excess Ni and Co. Both Ni and Co templatesmore » were found to have similarly positive impacts, although specific differences between the two systems are revealed. In single-cell electrolysis testing, nanowires exceeded the performance of Ir nanoparticles by 4-5 times, suggesting that significant reductions in catalyst loading are possible without compromising performance.« less
Evo-Devo-EpiR: a genome-wide search platform for epistatic control on the evolution of development.
Jiang, Libo; Zhang, Miaomiao; Sang, Mengmeng; Ye, Meixia; Wu, Rongling
2017-09-01
Evo-devo is a theory proposed to study how phenotypes evolve by comparing the developmental processes of different organisms or the same organism experiencing changing environments. It has been recognized that nonallelic interactions at different genes or quantitative trait loci, known as epistasis, may play a pivotal role in the evolution of development, but it has proven difficult to quantify and elucidate this role into a coherent picture. We implement a high-dimensional genome-wide association study model into the evo-devo paradigm and pack it into the R-based Evo-Devo-EpiR, aimed at facilitating the genome-wide landscaping of epistasis for the diversification of phenotypic development. By analyzing a high-throughput assay of DNA markers and their pairs simultaneously, Evo-Devo-EpiR is equipped with a capacity to systematically characterize various epistatic interactions that impact on the pattern and timing of development and its evolution. Enabling a global search for all possible genetic interactions for developmental processes throughout the whole genome, Evo-Devo-EpiR provides a computational tool to illustrate a precise genotype-phenotype map at interface between epistasis, development and evolution. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Beaulieu, Jeremy M; O'Meara, Brian C; Crane, Peter; Donoghue, Michael J
2015-09-01
Dating analyses based on molecular data imply that crown angiosperms existed in the Triassic, long before their undisputed appearance in the fossil record in the Early Cretaceous. Following a re-analysis of the age of angiosperms using updated sequences and fossil calibrations, we use a series of simulations to explore the possibility that the older age estimates are a consequence of (i) major shifts in the rate of sequence evolution near the base of the angiosperms and/or (ii) the representative taxon sampling strategy employed in such studies. We show that both of these factors do tend to yield substantially older age estimates. These analyses do not prove that younger age estimates based on the fossil record are correct, but they do suggest caution in accepting the older age estimates obtained using current relaxed-clock methods. Although we have focused here on the angiosperms, we suspect that these results will shed light on dating discrepancies in other major clades. ©The Author(s) 2015. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Pandey, Puran; Kunwar, Sundar; Sui, Mao; Bastola, Sushil; Lee, Jihoon
2017-01-01
Multi-metallic alloy nanoparticles (NPs) can offer additional opportunities for modifying the electronic, optical and catalytic properties by the control of composition, configuration and size of individual nanostructures that are consisted of more than single element. In this paper, the fabrication of bimetallic Pd-Ag NPs is systematically demonstrated via the solid state dewetting of bilayer thin films on c-plane sapphire by governing the temperature, time as well as composition. The composition of Pd-Ag bilayer remarkably affects the morphology of alloy nanostructures, in which the higher Ag composition, i.e. Pd0.25Ag0.75, leads to the enhanced dewetting of bilayers whereas the higher Pd composition (Pd0.75Ag0.25) hinders the dewetting. Depending on the annealing temperature, Pd-Ag alloy nanostructures evolve with a series of configurations, i.e. nucleation of voids, porous network, elongated nanoclusters and round alloy NPs. In addition, with the annealing time set, the gradual configuration transformation from the elongated to round alloy NPs as well as size reduction is demonstrated due to the enhanced diffusion and sublimation of Ag atoms. The evolution of various morphology of Pd-Ag nanostructures is described based on the surface diffusion and inter-diffusion of Pd and Ag adatoms along with the Ag sublimation, Rayleigh instability and energy minimization mechanism. The reflectance spectra of bimetallic Pd-Ag nanostructures exhibit various quadrupolar and dipolar resonance peaks, peak shifts and absorption dips owing to the surface plasmon resonance of nanostructures depending on the surface morphology. The intensity of reflectance spectra is gradually decreased along with the surface coverage and NP size evolution. The absorption dips are red-shifted towards the longer wavelength for the larger alloy NPs and vice-versa.
Si, L; Winzenberg, T M; Palmer, A J
2014-01-01
This review was aimed at the evolution of health economic models used in evaluations of clinical approaches aimed at preventing osteoporotic fractures. Models have improved, with medical continuance becoming increasingly recognized as a contributor to health and economic outcomes, as well as advancements in epidemiological data. Model-based health economic evaluation studies are increasingly used to investigate the cost-effectiveness of osteoporotic fracture preventions and treatments. The objective of this study was to carry out a systematic review of the evolution of health economic models used in the evaluation of osteoporotic fracture preventions. Electronic searches within MEDLINE and EMBASE were carried out using a predefined search strategy. Inclusion and exclusion criteria were used to select relevant studies. References listed of included studies were searched to identify any potential study that was not captured in our electronic search. Data on country, interventions, type of fracture prevention, evaluation perspective, type of model, time horizon, fracture sites, expressed costs, types of costs included, and effectiveness measurement were extracted. Seventy-four models were described in 104 publications, of which 69% were European. Earlier models focused mainly on hip, vertebral, and wrist fracture, but later models included multiple fracture sites (humerus, pelvis, tibia, and other fractures). Modeling techniques have evolved from simple decision trees, through deterministic Markov processes to individual patient simulation models accounting for uncertainty in multiple parameters. Treatment continuance has been increasingly taken into account in the models in the last decade. Models have evolved in their complexity and emphasis, with medical continuance becoming increasingly recognized as a contributor to health and economic outcomes. This evolution may be driven in part by the desire to capture all the important differentiating characteristics of medications under scrutiny, as well as the advancement in epidemiological data relevant to osteoporosis fractures.
[Metaplasic Paneth cells in ulcerative colitis].
Bedini, Oscar Alfredo; Naves, Ariel; San Miguel, Patricia; Quispe, Arturo; Guida, Carolina
2014-01-01
Paneth cells are normally present in small intestine, but its appearance in other areas of the gastrointestinal tract is related to chronic inflammatory processes. In our study we retrospectively examined 29 patients with diagnosis of ulcerative colitis, from the files of Instituto de Histopatología de Rosario, and from the casuistry of two authors (O.B. and P.S.M.), during two years. Biopsies corresponded to rectal or sigmoid mucosa and were stained with H.E. Distal Paneth cells in rectum and/or sigmoid colon were found in 60% of patients. This finding was related to the time of evolution of the disease (median 7 years for patients with Paneth cells and 3 years for patients without Paneth cells). With more time of evolution, there were more number of affected crypts and more number of Paneth cells. Some of the patients with longer evolution had 2-5 crypts with Paneth cells (up to 11 Paneth cells). When the time of evolution of the disease was longer, we found an irregular distribution of Paneth cells, with migration from the depth of the crypt to highest crypt levels. There was a relationship between the number of Paneth cells and the degree of leukocyte infiltration of the mucosa. We observed a direct correlation of the presence of Paneth cells with the time of evolution of the disease and with the leukocyte infiltration of the mucosa.
Multi-Agent Simulations of Earth's Dynamics: Towards a Virtual Laboratory for Plate Tectonics
NASA Astrophysics Data System (ADS)
Grigne, C.; Combes, M.; Tisseau, C.; LeYaouanq, S.; Parenthoen, M.; Tisseau, J.
2012-12-01
MACMA (Multi-Agent Convective MAntle) is a new tool developed at Laboratoire Domaines Océaniques (UMR CNRS 6538) and CERV-LabSTICC (Centre Européen de Réalité Virtuelle, UMR CNRS 6285) to simulate evolutive plates tectonics and mantle convection in a 2-D cylindrical geometry (Combes et al., 2012). In this approach, ridges, subduction zones, continents and convective cells are agents, whose behavior is controlled by analytical and phenomenological laws. These agents are autonomous entities which collect information from their environment and interact with each other. The dynamics of the system is mainly based on a force balance on each plate, that accounts for slab pull, ridge push, bending dissipation and viscous convective drag. Insulating continents are accounted for. Tectonic processes such as trench migration, plate suturing or continental breakup are controlled by explicit parameterizations. A heat balance is used to compute Earth's thermal evolution as a function of seafloor age distribution. We thereby obtain an evolutive system where the geometry and the number of tectonic plates are not imposed but emerge naturally from its dynamical history. Our approach has a very low computational cost and allows us to study the effect of a wide range of input parameters on the long-term thermal evolution of the Earth. MACMA can thus be seen as a 'plate tectonics virtual laboratory'. We can test not only the effect of input parameters, such as mantle initial temperature and viscosity, initial plate tectonics configuration, number and geometry of continents etc., but also study the effect of the analytical and empirical rules that we are using to describe the system. These rules can be changed at any time, and MACMA is an evolutive tool that can easily integrate new behavioral laws. Even poorly understood processes, that cannot be accounted for with differential equations, can be studied with this virtual laboratory. For Earth-like input parameters, MACMA yields plate velocities and heat flux that are in good agreement with observations. The long-term thermal evolution of the Earth obtained with our model shows a slow monotonous decrease of mantle mean temperature, with a cooling rate of around 50-100 K per billion years, which is in good agreement with petrological and geochemical constraints. Heat flux and plate velocities show a more irregular evolution, because tectonic events, such as a continental breakup, give rise to abrupt changes in Earth's surface dynamics and heat loss. Therefore MACMA is a powerful tool to study in a systematic way the effect of local events (subduction initiation, continental breakup, ridge vanishing) on plate reorganizations and global surface dynamics.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xi, Xiaoning; Tittmann, Bernhard; Kim, Seong H.
An atomic force microscopy based nanoindentation method was employed to study how the structure of cellulose microfibril packing and matrix polymers affect elastic modulus of fully hydrated primary plant cell walls. The isolated, single-layered abaxial epidermis cell wall of an onion bulb was used as a test system since the cellulose microfibril packing in this cell wall is known to vary systematically from inside to outside scales and the most abundant matrix polymer, pectin, can easily be altered through simple chemical treatments such as ethylenediaminetetraacetic acid and calcium ions. Experimental results showed that the pectin network variation has significant impactsmore » on the cell wall modulus, and not the cellulose microfibril packing.« less
Gralewski, Jonathon H; Post, Ginell R; van Rhee, Frits; Yuan, Youzhong
2018-02-20
Plasma cell myeloma (PCM) is a neoplasm of terminally differentiated B lymphocytes with molecular heterogeneity. Although therapy-related myeloid neoplasms are common in plasma cell myeloma patients after chemotherapy, transdifferentiation of plasma cell myeloma into myeloid neoplasms has not been reported in literature. Here we report a very rare case of myeloid neoplasm transformed from plasma cell myeloma. A 60-year-old man with a history of plasma cell myeloma with IGH-MAF gene rearrangement and RAS/RAF mutations developed multiple soft tissue lesions one year following melphalan-based chemotherapy and autologous stem cell transplant. Morphological and immunohistochemical characterization of the extramedullary disease demonstrated that the tumor cells were derived from the monocyte-macrophage lineage. Next generation sequencing (NGS) studies detected similar clonal aberrations in the diagnostic plasma cell population and post-therapy neoplastic cells, including IGH-MAF rearrangement, multiple genetic mutations in RAS signaling pathway proteins, and loss of tumor suppressor genes. Molecular genetic analysis also revealed unique genomic alterations in the transformed tumor cells, including gain of NF1 and loss of TRAF3. To our knowledge, this is the first case of myeloid sarcoma transdifferentiated from plasma cell neoplasm. Our findings in this unique case suggest clonal evolution of plasma cell myeloma to myeloma neoplasm and the potential roles of abnormal RAS/RAF signaling pathway in lineage switch or transdifferentiation.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bi, Xuanxuan; Wang, Rongyue; Ma, Lu
In sodium–oxygen (Na–O2) batteries, multiple discharge products have been observed by different research groups. Given the fact that different materials, gas supplies, and cell configurations are used by different groups, it is a great challenge to draw a clear conclusion on the formation of the different products. Here, two different cell setups are used to investigate the cell chemistries of Na–O2 batteries. With the same materials and gas supplies, a peroxide-based product is observed in a glass chamber cell and a superoxide-based product is observed in a stainless-steel cell. Ex situ high-energy X-ray diffraction (HEXRD) and Raman spectroscopy are performedmore » to investigate the structure and composition of the product. In addition, in situ XRD is used to investigate the structure evolution of the peroxide-based product. The findings highlight the importance of the cell design and emphasize the critical environment of the formation of the discharge products of Na–O2 batteries.« less
Miyaoka, Yuichiro; Berman, Jennifer R; Cooper, Samantha B; Mayerl, Steven J; Chan, Amanda H; Zhang, Bin; Karlin-Neumann, George A; Conklin, Bruce R
2016-03-31
Precise genome-editing relies on the repair of sequence-specific nuclease-induced DNA nicking or double-strand breaks (DSBs) by homology-directed repair (HDR). However, nonhomologous end-joining (NHEJ), an error-prone repair, acts concurrently, reducing the rate of high-fidelity edits. The identification of genome-editing conditions that favor HDR over NHEJ has been hindered by the lack of a simple method to measure HDR and NHEJ directly and simultaneously at endogenous loci. To overcome this challenge, we developed a novel, rapid, digital PCR-based assay that can simultaneously detect one HDR or NHEJ event out of 1,000 copies of the genome. Using this assay, we systematically monitored genome-editing outcomes of CRISPR-associated protein 9 (Cas9), Cas9 nickases, catalytically dead Cas9 fused to FokI, and transcription activator-like effector nuclease at three disease-associated endogenous gene loci in HEK293T cells, HeLa cells, and human induced pluripotent stem cells. Although it is widely thought that NHEJ generally occurs more often than HDR, we found that more HDR than NHEJ was induced under multiple conditions. Surprisingly, the HDR/NHEJ ratios were highly dependent on gene locus, nuclease platform, and cell type. The new assay system, and our findings based on it, will enable mechanistic studies of genome-editing and help improve genome-editing technology.
Yoshizawa, Kazunori; Johnson, Kevin P
2008-02-01
We evaluated the higher level classification within the family Psocidae (Insecta: Psocodea: 'Psocoptera') based on combined analyses of nuclear 18S, Histone 3, wingless and mitochondrial 12S, 16S and COI gene sequences. Various analyses (inclusion/exclusion of incomplete taxa and/or rapidly evolving genes, data partitioning, and analytical method selection) all provided similar results, which were generally concordant with relationships inferred using morphological observations. Based on the phylogenetic trees estimated for Psocidae, we propose a revised higher level classification of this family, although uncertainty still exists regarding some aspects of this classification. This classification includes a basal division into two subfamilies, 'Amphigerontiinae' (possibly paraphyletic) and Psocinae. The Amphigerontiinae is divided into the tribes Kaindipsocini (new tribe), Blastini, Amphigerontini, and Stylatopsocini. Psocinae is divided into the tribes 'Ptyctini' (probably paraphyletic), Psocini, Atrichadenotecnini (new tribe), Sigmatoneurini, Metylophorini, and Thyrsophorini (the latter includes the taxon previously recognized as Cerastipsocini). We examined the evolution of symmetric/asymmetric male genitalia over this tree and found this character to be quite homoplasious.
Dynamics of morphological evolution in experimental Escherichia coli populations.
Cui, F; Yuan, B
2016-08-30
Here, we applied a two-stage clonal expansion model of morphological (cell-size) evolution to a long-term evolution experiment with Escherichia coli. Using this model, we derived the incidence function of the appearance of cell-size stability, the waiting time until this morphological stability, and the conditional and unconditional probabilities of morphological stability. After assessing the parameter values, we verified that the calculated waiting time was consistent with the experimental results, demonstrating the effectiveness of the two-stage model. According to the relative contributions of parameters to the incidence function and the waiting time, cell-size evolution is largely determined by the promotion rate, i.e., the clonal expansion rate of selectively advantageous organisms. This rate plays a prominent role in the evolution of cell size in experimental populations, whereas all other evolutionary forces were found to be less influential.
NASA Astrophysics Data System (ADS)
Takagi, R.; Obara, K.; Uchida, N.
2017-12-01
Understanding slow earthquake activity improves our knowledge of slip behavior in brittle-ductile transition zone and subduction process including megathrust earthquakes. In order to understand overall picture of slow slip activity, it is important to make a comprehensive catalog of slow slip events (SSEs). Although short-term SSEs have been detected by GNSS and tilt meter records systematically, analysis of long-term slow slip events relies on individual slip inversions. We develop an algorism to systematically detect long-term SSEs and estimate source parameters of the SSEs using GNSS data. The algorism is similar to GRiD-MT (Tsuruoka et al., 2009), which is grid-based automatic determination of moment tensor solution. Instead of moment tensor fitting to long period seismic records, we estimate parameters of a single rectangle fault to fit GNSS displacement time series. First, we make a two dimensional grid covering possible location of SSE. Second, we estimate best-fit parameters (length, width, slip, and rake) of the rectangle fault at each grid point by an iterative damped least square method. Depth, strike, and dip are fixed on the plate boundary. Ramp function with duration of 300 days is used for expressing time evolution of the fault slip. Third, a grid maximizing variance reduction is selected as a candidate of long-term SSE. We also search onset of ramp function based on the grid search. We applied the method to GNSS data in southwest Japan to detect long-term SSEs in Nankai subduction zone. With current selection criteria, we found 13 events with Mw6.2-6.9 in Hyuga-nada, Bungo channel, and central Shikoku from 1998 to 2015, which include unreported events. Key finding is along strike migrations of long-term SSEs from Hyuga-nada to Bungo channel and from Bungo channel to central Shikoku. In particular, three successive events migrating northward in Hyuga-nada preceded the 2003 Bungo channel SSE, and one event in central Shikoku followed the 2003 SSE in Bungo channel. The space-time dimensions of the possible along-strike migration are about 300km in length and 6 years in time. Systematic detection with assumptions of various durations in the time evolution of SSE may improve the picture of SSE activity and possible interaction with neighboring SSEs.
Application of stem cells in targeted therapy of breast cancer: a systematic review.
Madjd, Zahra; Gheytanchi, Elmira; Erfani, Elham; Asadi-Lari, Mohsen
2013-01-01
The aim of this systematic review was to investigate whether stem cells could be effectively applied in targeted therapy of breast cancer. A systematic literature search was performed for original articles published from January 2007 until May 2012. Nine studies met the inclusion criteria for phase I or II clinical trials, of which three used stem cells as vehicles, two trials used autologous hematopoetic stem cells and in four trials cancer stem cells were targeted. Mesenchymal stem cells (MSCs) were applied as cellular vehicles to transfer therapeutic agents. Cell therapy with MSC can successfully target resistant cancers. Cancer stem cells were selectively targeted via a proteasome-dependent suicide gene leading to tumor regression. Wnt/β-catenin signaling pathway has been also evidenced to be an attractive CSC-target. This systematic review focused on two different concepts of stem cells and breast cancer marking a turning point in the trials that applied stem cells as cellular vehicles for targeted delivery therapy as well as CSC-targeted therapies. Applying stem cells as targeted therapy could be an effective therapeutic approach for treatment of breast cancer in the clinic and in therapeutic marketing; however this needs to be confirmed with further clinical investigations.
Building better lithium-sulfur batteries: from LiNO3 to solid oxide catalyst
NASA Astrophysics Data System (ADS)
Ding, Ning; Zhou, Lan; Zhou, Changwei; Geng, Dongsheng; Yang, Jin; Chien, Sheau Wei; Liu, Zhaolin; Ng, Man-Fai; Yu, Aishui; Hor, T. S. Andy; Sullivan, Michael B.; Zong, Yun
2016-09-01
Lithium nitrate (LiNO3) is known as an important electrolyte additive in lithium-sulfur (Li-S) batteries. The prevailing understanding is that LiNO3 reacts with metallic lithium anode to form a passivation layer which suppresses redox shuttles of lithium polysulfides, enabling good rechargeability of Li-S batteries. However, this view is seeing more challenges in the recent studies, and above all, the inability of inhibiting polysulfide reduction on Li anode. A closely related issue is the progressive reduction of LiNO3 on Li anode which elevates internal resistance of the cell and compromises its cycling stability. Herein, we systematically investigated the function of LiNO3 in redox-shuttle suppression, and propose the suppression as a result of catalyzed oxidation of polysulfides to sulfur by nitrate anions on or in the proximity of the electrode surface upon cell charging. This hypothesis is supported by both density functional theory calculations and the nitrate anions-suppressed self-discharge rate in Li-S cells. The catalytic mechanism is further validated by the use of ruthenium oxide (RuO2, a good oxygen evolution catalyst) on cathode, which equips the LiNO3-free cell with higher capacity and improved capacity retention over 400 cycles.
Building better lithium-sulfur batteries: from LiNO3 to solid oxide catalyst
Ding, Ning; Zhou, Lan; Zhou, Changwei; Geng, Dongsheng; Yang, Jin; Chien, Sheau Wei; Liu, Zhaolin; Ng, Man-Fai; Yu, Aishui; Hor, T. S. Andy; Sullivan, Michael B.; Zong, Yun
2016-01-01
Lithium nitrate (LiNO3) is known as an important electrolyte additive in lithium-sulfur (Li-S) batteries. The prevailing understanding is that LiNO3 reacts with metallic lithium anode to form a passivation layer which suppresses redox shuttles of lithium polysulfides, enabling good rechargeability of Li-S batteries. However, this view is seeing more challenges in the recent studies, and above all, the inability of inhibiting polysulfide reduction on Li anode. A closely related issue is the progressive reduction of LiNO3 on Li anode which elevates internal resistance of the cell and compromises its cycling stability. Herein, we systematically investigated the function of LiNO3 in redox-shuttle suppression, and propose the suppression as a result of catalyzed oxidation of polysulfides to sulfur by nitrate anions on or in the proximity of the electrode surface upon cell charging. This hypothesis is supported by both density functional theory calculations and the nitrate anions-suppressed self-discharge rate in Li-S cells. The catalytic mechanism is further validated by the use of ruthenium oxide (RuO2, a good oxygen evolution catalyst) on cathode, which equips the LiNO3-free cell with higher capacity and improved capacity retention over 400 cycles. PMID:27629986
Eswaran, Jeyanthy; Li, Da-Qiang; Shah, Anil; Kumar, Rakesh
2012-07-15
The evolution of cancer cells involves deregulation of highly regulated fundamental pathways that are central to normal cellular architecture and functions. p21-activated kinase 1 (PAK1) was initially identified as a downstream effector of the GTPases Rac and Cdc42. Subsequent studies uncovered a variety of new functions for this kinase in growth factor and steroid receptor signaling, cytoskeleton remodeling, cell survival, oncogenic transformation, and gene transcription, largely through systematic discovery of its direct, physiologically relevant substrates. PAK1 is widely upregulated in several human cancers, such as hormone-dependent cancer, and is intimately linked to tumor progression and therapeutic resistance. These exciting developments combined with the kinase-independent role of PAK1-centered phenotypic signaling in cancer cells elevated PAK1 as an attractive drug target. Structural and biochemical studies revealed the precise mechanism of PAK1 activation, offering the possibility to develop PAK1-targeted cancer therapeutic approaches. In addition, emerging reports suggest the potential of PAK1 and its specific phosphorylated substrates as cancer prognostic markers. Here, we summarize recent findings about the PAK1 molecular pathways in human cancer and discuss the current status of PAK1-targeted anticancer therapies.
Rapid detection of food pathogens using RNA aptamers-immobilized slide.
Maeng, Jin-Soo; Kim, Namsoo; Kim, Chong-Tai; Han, Seung Ryul; Lee, Young Ju; Lee, Seong-Wook; Lee, Myung-Hyun; Cho, Yong-Jin
2012-07-01
The purpose of this study was to develop a simple and rapid detection system for foodborne bacteria, which consisted of an optical microscope and its slide chip with artificial antibodies, or RNA aptamers. From an RNA pool, three each RNA aptamers were built by the method of SELEX (systematic evolution of ligands by exponential enrichment) for components of cell wall, LPS (lipopolysaccharide) from E. coli O157:H7, teichoic acid from Staphylococcus aureus and a cell membrane protein of OmpC from Salmonella typhimurium, respectively. These aptamers were hybridized with thiol-conjugated 16 dT-linker molecules in order to be immobilized on silver surface which was, in advance, fabricated on glass slide, using a spin-coating method. To confirm that each aptamers retained its specific binding activities to their antigenic live bacteria, microscopic view of bound cells immobilized on silver film were observed. Furthermore, we observed the fluorescence-emitting bacteria-aptamer complex immobilized on silver film after adding RNA aptamers hybridized with fluorophore, FAM-conjugated 16 dT-linker molecules. As a result, the RNA aptamers-immobilized slide system developed in this study was a useful new tool to rapidly monitor individual food pathogens.
NASA Astrophysics Data System (ADS)
Mursula, K.; Virtanen, I. I.
2012-08-01
We reanalyze the observations of the heliospheric magnetic field (HMF) made by the Pioneer 10 and 11 and Voyager 1 and 2 heliospheric probes since 1972, and calculate the HMF sector occurrence ratios and tangential component strengths in the different regions of the heliosphere. Observations at the distant probes and at 1 AU show a very consistent picture of the HMF sector structure in the entire heliosphere, and even beyond the termination shock. HMF observations by the probes also support the southward shift of the heliospheric current sheet (the bashful ballerina phenomenon), which is observed earlier at 1-2 AU by the Ulysses probe and Earth-orbiting satellites, and verify the HCS shift over a wide range of radial distances until the distant heliosphere. Pioneer 11 and Voyager 1 show that the development of northern polar coronal holes was very systematic and active during all the four solar minima since mid-1970s, while Voyager 2 observations show a less systematic and delayed development of southern coronal holes in 1980s, 1990s and 2000s. This delay in the evolution of southern coronal holes with respect to the rapid and systematic evolution of northern coronal holes leads to a larger extent of northern coronal holes and the southward shift of the HCS for a few years in the late declining phase of each solar cycle. Although evidence for the connection between the different evolution of polar coronal holes and the bashful ballerina phenomenon is obtained here only for three solar cycles, this may be a common pattern for solar coronal hole evolution since the southward shift of the HCS has occurred at least since solar cycle 16.
Lee, Sang-Woo; Morishita, Yoshihiro
2017-07-01
Cell competition is a phenomenon originally described as the competition between cell populations with different genetic backgrounds; losing cells with lower fitness are eliminated. With the progress in identification of related molecules, some reports described the relevance of cell mechanics during elimination. Furthermore, recent live imaging studies have shown that even in tissues composed of genetically identical cells, a non-negligible number of cells are eliminated during growth. Thus, mechanical cell elimination (MCE) as a consequence of mechanical cellular interactions is an unavoidable event in growing tissues and a commonly observed phenomenon. Here, we studied MCE in a genetically-homogeneous tissue from the perspective of tissue growth efficiency and homeostasis. First, we propose two quantitative measures, cell and tissue fitness, to evaluate cellular competitiveness and tissue growth efficiency, respectively. By mechanical tissue simulation in a pure population where all cells have the same mechanical traits, we clarified the dependence of cell elimination rate or cell fitness on different mechanical/growth parameters. In particular, we found that geometrical (specifically, cell size) and mechanical (stress magnitude) heterogeneities are common determinants of the elimination rate. Based on these results, we propose possible mechanical feedback mechanisms that could improve tissue growth efficiency and density/stress homeostasis. Moreover, when cells with different mechanical traits are mixed (e.g., in the presence of phenotypic variation), we show that MCE could drive a drastic shift in cell trait distribution, thereby improving tissue growth efficiency through the selection of cellular traits, i.e. intra-tissue "evolution". Along with the improvement of growth efficiency, cell density, stress state, and phenotype (mechanical traits) were also shown to be homogenized through growth. More theoretically, we propose a mathematical model that approximates cell competition dynamics, by which the time evolution of tissue fitness and cellular trait distribution can be predicted without directly simulating a cell-based mechanical model.
Comparative Planetary Mineralogy: Co, Ni Systematics in Chromite from Planetary Basalts
NASA Technical Reports Server (NTRS)
Karner, J. M.; Shearer, C. K.; Papike, J. J.; Righter,K.
2005-01-01
Spinel is a minor but important phase in planetary basalts because its variable composition often reflects basalt petrogenesis. For example, complicated zoning trends in spinel can give clues to melt evolution [1], and V concentrations in chromite lend insight into magma oxygen fugacity (fO2) conditions [2]. Nickel and Co are two elements that are commonly used as a measure of melt fractionation, and their partitioning between olivine and melt is fairly well understood. Less clear is their partitioning into spinel, although [3] has explored Ni and Co systematics in experimental charges. This study documents Ni and Co behavior in early crystallizing spinel (chromite) from several planetary basalts in an attempt to compare our results with [3], and also gain insight into basalt evolution on the three planets.
Patterson, Larissa B.; Bain, Emily J.; Parichy, David M.
2014-01-01
Fishes have diverse pigment patterns, yet mechanisms of pattern evolution remain poorly understood. In zebrafish, Danio rerio, pigment-cell autonomous interactions generate dark stripes of melanophores that alternate with light interstripes of xanthophores and iridophores. Here, we identify mechanisms underlying the evolution of a uniform pattern in D. albolineatus in which all three pigment cell classes are intermingled. We show that in this species xanthophores differentiate precociously over a wider area, and that cis regulatory evolution has increased expression of xanthogenic Colony Stimulating Factor-1 (Csf1). Expressing Csf1 similarly in D. rerio has cascading effects, driving the intermingling of all three pigment cell classes and resulting in the loss of stripes, as in D. albolineatus. Our results identify novel mechanisms of pattern development and illustrate how pattern diversity can be generated when a core network of pigment-cell autonomous interactions is coupled with changes in pigment cell differentiation. PMID:25374113
Optimal surveys for weak-lensing tomography
NASA Astrophysics Data System (ADS)
Amara, Adam; Réfrégier, Alexandre
2007-11-01
Weak-lensing surveys provide a powerful probe of dark energy through the measurement of the mass distribution of the local Universe. A number of ground-based and space-based surveys are being planned for this purpose. Here, we study the optimal strategy for these future surveys using the joint constraints on the equation-of-state parameter wn and its evolution wa as a figure of merit by considering power spectrum tomography. For this purpose, we first consider an `ideal' survey which is both wide and deep and exempt from systematics. We find that such a survey has great potential for dark energy studies, reaching 1σ precisions of 1 and 10 per cent on the two parameters, respectively. We then study the relative impact of various limitations by degrading this ideal survey. In particular, we consider the effect of sky coverage, survey depth, shape measurement systematics, photometric redshift systematics and uncertainties in the non-linear power spectrum predictions. We find that, for a given observing time, it is always advantageous to choose a wide rather than a deep survey geometry. We also find that the dark energy constraints from power spectrum tomography are robust to photometric redshift errors and catastrophic failures, if a spectroscopic calibration sample of 104-105 galaxies are available. The impact of these systematics is small compared to the limitations that come from potential uncertainties in the power spectrum, due to shear measurement and theoretical errors. To help the planning of future surveys, we summarize our results with comprehensive scaling relations which avoid the need for full Fisher matrix calculations.
Pan, Xinju; Zhou, Gang
2018-03-28
It is desirable, yet challenging, to utilize non-precious metals instead of noble-metals as efficient catalysts in the renewable energy manufacturing industry. Using first principles calculations, we study the structural characteristics of partially oxidized nickel-based nanoheterostructures (NiO/Ni NHSs), and the interfacial effects on hydrogen evolution. The origin of the enhanced hydrogen evolution performance is discussed at the microscopic level. This study identifies two types of active sites of the exposed Ni surface available for the hydrogen evolution reaction (HER). One is the hcp-hollow sites near the perimeter boundary that exhibit a more excellent HER performance than platinum (Pt), and the other the second nearest neighbor fcc-hollow sites away from the boundary that exhibit a similar performance to Pt. The interfacial effects result from the competitive charge transfer between NiO and Ni surfaces in NHSs, and enhance the reactivity of NiO/Ni NHSs by shifting the d-states of surface atoms down in energy. The illumination of the mechanism would be helpful for the design of more efficient and cheap transition metal-based catalysts.
Wiklander, Oscar P B; Bostancioglu, R Beklem; Welsh, Joshua A; Zickler, Antje M; Murke, Florian; Corso, Giulia; Felldin, Ulrika; Hagey, Daniel W; Evertsson, Björn; Liang, Xiu-Ming; Gustafsson, Manuela O; Mohammad, Dara K; Wiek, Constanze; Hanenberg, Helmut; Bremer, Michel; Gupta, Dhanu; Björnstedt, Mikael; Giebel, Bernd; Nordin, Joel Z; Jones, Jennifer C; El Andaloussi, Samir; Görgens, André
2018-01-01
Extracellular vesicles (EVs) can be harvested from cell culture supernatants and from all body fluids. EVs can be conceptually classified based on their size and biogenesis as exosomes and microvesicles. Nowadays, it is however commonly accepted in the field that there is a much higher degree of heterogeneity within these two subgroups than previously thought. For instance, the surface marker profile of EVs is likely dependent on the cell source, the cell's activation status, and multiple other parameters. Within recent years, several new methods and assays to study EV heterogeneity in terms of surface markers have been described; most of them are being based on flow cytometry. Unfortunately, such methods generally require dedicated instrumentation, are time-consuming and demand extensive operator expertise for sample preparation, acquisition, and data analysis. In this study, we have systematically evaluated and explored the use of a multiplex bead-based flow cytometric assay which is compatible with most standard flow cytometers and facilitates a robust semi-quantitative detection of 37 different potential EV surface markers in one sample simultaneously. First, assay variability, sample stability over time, and dynamic range were assessed together with the limitations of this assay in terms of EV input quantity required for detection of differently abundant surface markers. Next, the potential effects of EV origin, sample preparation, and quality of the EV sample on the assay were evaluated. The findings indicate that this multiplex bead-based assay is generally suitable to detect, quantify, and compare EV surface signatures in various sample types, including unprocessed cell culture supernatants, cell culture-derived EVs isolated by different methods, and biological fluids. Furthermore, the use and limitations of this assay to assess heterogeneities in EV surface signatures was explored by combining different sets of detection antibodies in EV samples derived from different cell lines and subsets of rare cells. Taken together, this validated multiplex bead-based flow cytometric assay allows robust, sensitive, and reproducible detection of EV surface marker expression in various sample types in a semi-quantitative way and will be highly valuable for many researchers in the EV field in different experimental contexts.
Classifying the evolutionary and ecological features of neoplasms
Maley, Carlo C.; Aktipis, Athena; Graham, Trevor A.; Sottoriva, Andrea; Boddy, Amy M.; Janiszewska, Michalina; Silva, Ariosto S.; Gerlinger, Marco; Yuan, Yinyin; Pienta, Kenneth J.; Anderson, Karen S.; Gatenby, Robert; Swanton, Charles; Posada, David; Wu, Chung-I; Schiffman, Joshua D.; Hwang, E. Shelley; Polyak, Kornelia; Anderson, Alexander R. A.; Brown, Joel S.; Greaves, Mel; Shibata, Darryl
2018-01-01
Neoplasms change over time through a process of cell-level evolution, driven by genetic and epigenetic alterations. However, the ecology of the microenvironment of a neoplastic cell determines which changes provide adaptive benefits. There is widespread recognition of the importance of these evolutionary and ecological processes in cancer, but to date, no system has been proposed for drawing clinically relevant distinctions between how different tumours are evolving. On the basis of a consensus conference of experts in the fields of cancer evolution and cancer ecology, we propose a framework for classifying tumours that is based on four relevant components. These are the diversity of neoplastic cells (intratumoural heterogeneity) and changes over time in that diversity, which make up an evolutionary index (Evo-index), as well as the hazards to neoplastic cell survival and the resources available to neoplastic cells, which make up an ecological index (Eco-index). We review evidence demonstrating the importance of each of these factors and describe multiple methods that can be used to measure them. Development of this classification system holds promise for enabling clinicians to personalize optimal interventions based on the evolvability of the patient’s tumour. The Evo- and Eco-indices provide a common lexicon for communicating about how neoplasms change in response to interventions, with potential implications for clinical trials, personalized medicine and basic cancer research. PMID:28912577
Kulinowski, Piotr; Dorożyński, Przemysław; Młynarczyk, Anna; Węglarz, Władysław P
2011-05-01
The purpose of the study was to present a methodology for the processing of Magnetic Resonance Imaging (MRI) data for the quantification of the dosage form matrix evolution during drug dissolution. The results of the study were verified by comparison with other approaches presented in literature. A commercially available, HPMC-based quetiapine fumarate tablet was studied with a 4.7T MR system. Imaging was performed inside an MRI probe-head coupled with a flow-through cell for 12 h in circulating water. The images were segmented into three regions using threshold-based segmentation algorithms due to trimodal structure of the image intensity histograms. Temporal evolution of dry glassy, swollen glassy and gel regions was monitored. The characteristic features were observed: initial high expansion rate of the swollen glassy and gel layers due to initial water uptake, dry glassy core disappearance and maximum area of swollen glassy region at 4 h, and subsequent gel layer thickness increase at the expense of swollen glassy layer. The temporal evolution of an HPMC-based tablet by means of noninvasive MRI integrated with USP Apparatus 4 was found to be consistent with both the theoretical model based on polymer disentanglement concentration and experimental VIS/FTIR studies.
NASA Astrophysics Data System (ADS)
Komori, S.; Kakeya, I.
2018-06-01
Doping evolution of the unconventional superconducting properties in BaBiO3-based compounds has yet to be clarified in detail due to the significant change of the oxygen concentration accompanied by the chemical substitution. We suggest that the carrier concentration of an unconventional superconductor, BaPb0.7Bi0.3O3‑δ , is controllable without inducing chemical or structural changes using an electric double-layer transistor structure. The critical temperature is found to decrease systematically with increasing carrier concentration.
Cause Analysis on the Void under Slabs of Cement Concrete Pavement
NASA Astrophysics Data System (ADS)
Wen, Li; Zhu, Guo Xin; Baozhu
2017-06-01
This paper made a systematic analysis on the influence of the construction, environment, water and loads on the void beneath road slabs, and also introduced the formation process of structural void and pumping void, and summarizes the deep reasons for the bottom of the cement concrete pavement. Based on the analysis above, this paper has found out the evolution law of the void under slabs which claimed that the void usually appeared in the slab corners and then the cross joint, resulting void in the four sides with the void area under the front slab larger than the rear one.
Intrinsically Disordered Proteins and the Origins of Multicellular Organisms
NASA Astrophysics Data System (ADS)
Dunker, A. Keith
In simple multicellular organisms all of the cells are in direct contact with the surrounding milieu, whereas in complex multicellular organisms some cells are completely surrounded by other cells. Current phylogenetic trees indicate that complex multicellular organisms evolved independently from unicellular ancestors about 10 times, and only among the eukaryotes, including once for animals, twice each for green, red, and brown algae, and thrice for fungi. Given these multiple independent evolutionary lineages, we asked two questions: 1. Which molecular functions underpinned the evolution of multicellular organisms?; and, 2. Which of these molecular functions depend on intrinsically disordered proteins (IDPs)? Compared to unicellularity, multicellularity requires the advent of molecules for cellular adhesion, for cell-cell communication and for developmental programs. In addition, the developmental programs need to be regulated over space and time. Finally, each multicellular organism has cell-specific biochemistry and physiology. Thus, the evolution of complex multicellular organisms from unicellular ancestors required five new classes of functions. To answer the second question we used Key-words in Swiss Protein ranked for associations with predictions of protein structure or disorder. With a Z-score of 18.8 compared to random-function proteins, à differentiation was the biological process most strongly associated with IDPs. As expected from this result, large numbers of individual proteins associated with differentiation exhibit substantial regions of predicted disorder. For the animals for which there is the most readily available data all five of the underpinning molecular functions for multicellularity were found to depend critically on IDP-based mechanisms and other evidence supports these ideas. While the data are more sparse, IDPs seem to similarly underlie the five new classes of functions for plants and fungi as well, suggesting that IDPs were indeed crucial for the evolution of complex multicellular organisms. These new findings necessitate a rethinking of the gene regulatory network models currently used to explain cellular differentiation and the evolution of complex multicellular organisms.
Wilson, J P; Fischer, W W
2011-03-01
The core of plant physiology is a set of functional solutions to a tradeoff between CO(2) acquisition and water loss. To provide an important evolutionary perspective on how the earliest land plants met this tradeoff, we constructed a mathematical model (constrained geometrically with measurements of fossils) of the hydraulic resistance of Asteroxylon, an Early Devonian plant. The model results illuminate the water transport physiology of one of the earliest vascular plants. Results show that Asteroxylon's vascular system contains cells with low hydraulic resistances; these resistances are low because cells were covered by scalariform pits, elliptical structures that permit individual cells to have large areas for water to pass from one cell to another. Asteroxylon could move a large amount of water quickly given its large pit areas; however, this would have left these plants particularly vulnerable to damage from excessive evapotranspiration. These results highlight a repeated pattern in plant evolution, wherein the evolution of highly conductive vascular tissue precedes the appearance of adaptations to increase water transport safety. Quantitative insight into the vascular transport of Asteroxylon also allows us to reflect on the quality of CO(2) proxy estimates based on early land plant fossils. Because Asteroxylon's vascular tissue lacked any safety features to prevent permanent damage, it probably used stomatal abundance and behavior to prevent desiccation. If correct, low stomatal frequencies in Asteroxylon reflect the need to limit evapotranspiration, rather than adaptation to high CO(2) concentrations in the atmosphere. More broadly, methods to reveal and understand water transport in extinct plants have a clear use in testing and bolstering fossil plant-based paleoclimate proxies. © 2011 Blackwell Publishing Ltd.
Biologic agents for anterior cruciate ligament healing: A systematic review
Di Matteo, Berardo; Loibl, Markus; Andriolo, Luca; Filardo, Giuseppe; Zellner, Johannes; Koch, Matthias; Angele, Peter
2016-01-01
AIM To systematically review the currently available literature concerning the application of biologic agents such as platelet-rich plasma (PRP) and stem cells to promote anterior cruciate ligament (ACL) healing. METHODS A systematic review of the literature was performed on the use of biologic agents (i.e., PRP or stem cells) to favor ACL healing during reconstruction or repair. The following inclusion criteria for relevant articles were used: Clinical reports of any level of evidence, written in English language, on the use of PRP or stem cells during ACL reconstruction/repair. Exclusion criteria were articles written in other languages, reviews, or studies analyzing other applications of PRP/stem cells in knee surgery not related to promoting ACL healing. RESULTS The database search identified 394 records that were screened. A total of 23 studies were included in the final analysis: In one paper stem cells were applied for ACL healing, in one paper there was a concomitant application of PRP and stem cells, whereas in the remaining 21 papers PRP was used. Based on the ACL injury pattern, two papers investigated biologic agents in ACL partial tears whereas 21 papers in ACL reconstruction. Looking at the quality of the available literature, 17 out of 21 studies dealing with ACL reconstruction were randomized controlled trials. Both studies on ACL repair were case series. CONCLUSION There is a paucity of clinical trials investigating the role of stem cells in promoting ACL healing both in case of partial and complete tears. The role of PRP is still controversial and the only advantage emerging from the literature is related to a better graft maturation over time, without documenting beneficial effects in terms of clinical outcome, bone-graft integration and prevention of bony tunnel enlargement. PMID:27672573
Transport phenomena in polymer electrolyte membrane fuel cells via voltage loss breakdown
NASA Astrophysics Data System (ADS)
Flick, Sarah; Dhanushkodi, Shankar R.; Mérida, Walter
2015-04-01
This study presents a voltage loss breakdown method based on in-situ experimental data to systematically analyze the different overpotentials of a polymer electrolyte membrane fuel cell. This study includes a systematic breakdown of the anodic overpotentials via the use of a reference electrode system. This work demonstrates the de-convolution of the individual overpotentials for both anode and cathode side, including the distinction between mass-transport overpotentials in cathode porous transport layer (PTL) and electrode, based on in-situ polarization tests under different operating conditions. This method is used to study the relationship between mass-transport losses inside the cathode catalyst layer (CL) and the PTL for both a single layer and two-layer PTL configuration. We conclude that the micro-porous layer (MPL) significantly improves the water removal within the cell, especially inside the cathode electrode, and therefore the mass transport within the cathode CL. This study supports the theory that the MPL on the cathode leads to an increase in water permeation from cathode to anode due to its function as a capillary barrier. This is reflected in increased anodic mass-transport overpotential, decreased ohmic losses and decreased cathode mass-transport losses, especially in the cathode electrode.
Abbasi, R; Marcus, J M
2015-11-01
Ocelli are serially repeated colour patterns on the wings of many butterflies. Eyespots are elaborate ocelli that function in predator avoidance and deterrence as well as in mate choice. A phylogenetic approach was used to study ocelli and eyespot evolution in Vanessa butterflies, a genus exhibiting diverse phenotypes among these serial homologs. Forty-four morphological characters based on eyespot number, arrangement, shape and the number of elements in each eyespot were defined and scored. Ocelli from eight wing cells on the dorsal and ventral surfaces of the forewing and hindwing were evaluated. The evolution of these characters was traced over a phylogeny of Vanessa based on 7750 DNA base pairs from 10 genes. Our reconstruction predicts that the ancestral Vanessa had 5 serially arranged ocelli on all four wing surfaces. The ancestral state on the dorsal forewing and ventral hindwing was ocelli arranged in two heterogeneous groups. On the dorsal hindwing, the ancestral state was either homogenous or ocelli arranged in two heterogeneous groups. On the ventral forewing, we determined that the ancestral state was organized into three heterogeneous groups. In Vanessa, almost all ocelli are individuated and capable of independent evolution relative to other colour patterns except for the ocelli in cells -1 and 0 on the dorsal and ventral forewings, which appear to be constrained to evolve in parallel. The genus Vanessa is a good model system for the study of serial homology and the interaction of selective forces with developmental architecture to produce diversity in butterfly colour patterns. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.
Yarmush, Martin L.; King, Kevin R.
2011-01-01
Living cells are remarkably complex. To unravel this complexity, living-cell assays have been developed that allow delivery of experimental stimuli and measurement of the resulting cellular responses. High-throughput adaptations of these assays, known as living-cell microarrays, which are based on microtiter plates, high-density spotting, microfabrication, and microfluidics technologies, are being developed for two general applications: (a) to screen large-scale chemical and genomic libraries and (b) to systematically investigate the local cellular microenvironment. These emerging experimental platforms offer exciting opportunities to rapidly identify genetic determinants of disease, to discover modulators of cellular function, and to probe the complex and dynamic relationships between cells and their local environment. PMID:19413510
NASA Astrophysics Data System (ADS)
Xu, Liangfei; Reimer, Uwe; Li, Jianqiu; Huang, Haiyan; Hu, Zunyan; Jiang, Hongliang; Janßen, Holger; Ouyang, Minggao; Lehnert, Werner
2018-02-01
City buses using polymer electrolyte membrane (PEM) fuel cells are considered to be the most likely fuel cell vehicles to be commercialized in China. The technical specifications of the fuel cell systems (FCSs) these buses are equipped with will differ based on the powertrain configurations and vehicle control strategies, but can generally be classified into the power-follow and soft-run modes. Each mode imposes different levels of electrochemical stress on the fuel cells. Evaluating the aging behavior of fuel cell stacks under the conditions encountered in fuel cell buses requires new durability test protocols based on statistical results obtained during actual driving tests. In this study, we propose a systematic design method for fuel cell durability test protocols that correspond to the power-follow mode based on three parameters for different fuel cell load ranges. The powertrain configurations and control strategy are described herein, followed by a presentation of the statistical data for the duty cycles of FCSs in one city bus in the demonstration project. Assessment protocols are presented based on the statistical results using mathematical optimization methods, and are compared to existing protocols with respect to common factors, such as time at open circuit voltage and root-mean-square power.
The functional basis of adaptive evolution in chemostats.
Gresham, David; Hong, Jungeui
2015-01-01
Two of the central problems in biology are determining the molecular basis of adaptive evolution and understanding how cells regulate their growth. The chemostat is a device for culturing cells that provides great utility in tackling both of these problems: it enables precise control of the selective pressure under which organisms evolve and it facilitates experimental control of cell growth rate. The aim of this review is to synthesize results from studies of the functional basis of adaptive evolution in long-term chemostat selections using Escherichia coli and Saccharomyces cerevisiae. We describe the principle of the chemostat, provide a summary of studies of experimental evolution in chemostats, and use these studies to assess our current understanding of selection in the chemostat. Functional studies of adaptive evolution in chemostats provide a unique means of interrogating the genetic networks that control cell growth, which complements functional genomic approaches and quantitative trait loci (QTL) mapping in natural populations. An integrated approach to the study of adaptive evolution that accounts for both molecular function and evolutionary processes is critical to advancing our understanding of evolution. By renewing efforts to integrate these two research programs, experimental evolution in chemostats is ideally suited to extending the functional synthesis to the study of genetic networks. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.
Abreu-Sepulveda, Maria A.; Dhital, Chetan; Huq, Ashfia; ...
2016-07-30
The effect due to systematic substitution of cobalt by iron in La 0.6Ca 0.4Co 1-xFe xO 3 towards the oxygen evolution reaction(OER) in alkaline media has been investigated. We synthesized these compounds by a facile glycine-nitrate synthesis and the phase formation was confirmed by X-ray diffraction and Neutron Diffraction elemental analysis. The apparent OER activity was evaluated by quasi steady state current measurements in alkaline media using a traditional three-electrode cell. X-ray photoelectron spectroscopy shows iron substitution causes an increase in the surface concentration of various cobalt oxidation states. Tafel slope in the vicinity of 60 mV/decade and electrochemical reactionmore » order towards OH- near unity were achieved for the unsubstituted La 0.6Ca 0.4CoO 3. Moreover, a decrease in the Tafel slope to 49 mV/decade was observed when iron is substituted in high amounts in the perovskite structure. The area specific current density showed dependence on the Fe fraction, however the relationship of specific current density with Fe fraction is not linear. High Fe substitutions, La 0.6Ca 0.4Co 0.2Fe 0.8O 3 and La 0.6Ca 0.4Co 0.1Fe 0.9O 3 showed higher area specific activity towards OER than La 0.6Ca 0.4CoO 3 or La 0.6Ca 0.4FeO 3. Finally, we believe iron inclusion in the cobalt sites of the perovskite helps decrease the electron transfer barrier and facilitates the formation of cobalt-hydroxide at the surface. Possible OER mechanisms based on the observed kinetic parameters will be discussed.« less
On the evolution of developmental mechanisms: Divergent polarities in leaf growth as a case study.
Gupta, Mainak Das; Nath, Utpal
2016-01-01
Most model plants used to study leaf growth share a common developmental mechanism, namely basipetal growth polarity, wherein the distal end differentiates first with progressively more proliferative cells toward the base. Therefore, this base-to-tip growth pattern has served as a paradigm to explain leaf growth and also formed the basis for several computational models. However, our recent report in The Plant Cell on the investigation of leaf growth in 75 eudicot species covering a wide range of eudicot families showed that leaves grow with divergent polarities in the proximo-distal axis or without any obvious polarity. This divergence in growth polarity is linked to the expression divergence of a conserved microRNA-transcription factor module. This study raises several questions on the evolutionary origin of leaf growth pattern, such as 'when and why in evolution did the divergent growth polarities arise?' and 'what were the molecular changes that led to this divergence?'. Here, we discuss a few of these questions in some detail.
Nikolov, Svetoslav; Santos, Guido; Wolkenhauer, Olaf; Vera, Julio
2018-02-01
Mathematical modeling of cell differentiated in colonic crypts can contribute to a better understanding of basic mechanisms underlying colonic tissue organization, but also its deregulation during carcinogenesis and tumor progression. Here, we combined bifurcation analysis to assess the effect that time delay has in the complex interplay of stem cells and semi-differentiated cells at the niche of colonic crypts, and systematic model perturbation and simulation to find model-based phenotypes linked to cancer progression. The models suggest that stem cell and semi-differentiated cell population dynamics in colonic crypts can display chaotic behavior. In addition, we found that clinical profiling of colorectal cancer correlates with the in silico phenotypes proposed by the mathematical model. Further, potential therapeutic targets for chemotherapy resistant phenotypes are proposed, which in any case will require experimental validation.
Tack, Ignace L M M; Logist, Filip; Noriega Fernández, Estefanía; Van Impe, Jan F M
2015-02-01
Traditional kinetic models in predictive microbiology reliably predict macroscopic dynamics of planktonically-growing cell cultures in homogeneous liquid food systems. However, most food products have a semi-solid structure, where microorganisms grow locally in colonies. Individual colony cells exhibit strongly different and non-normally distributed behavior due to local nutrient competition. As a result, traditional models considering average population behavior in a homogeneous system do not describe colony dynamics in full detail. To incorporate local resource competition and individual cell differences, an individual-based modeling approach has been applied to Escherichia coli K-12 MG1655 colonies, considering the microbial cell as modeling unit. The first contribution of this individual-based model is to describe single colony growth under nutrient-deprived conditions. More specifically, the linear and stationary phase in the evolution of the colony radius, the evolution from a disk-like to branching morphology, and the emergence of a starvation zone in the colony center are simulated and compared to available experimental data. These phenomena occur earlier at more severe nutrient depletion conditions, i.e., at lower nutrient diffusivity and initial nutrient concentration in the medium. Furthermore, intercolony interactions have been simulated. Higher inoculum densities lead to stronger intercolony interactions, such as colony merging and smaller colony sizes, due to nutrient competition. This individual-based model contributes to the elucidation of characteristic experimentally observed colony behavior from mechanistic information about cellular physiology and interactions. Copyright © 2014 Elsevier Ltd. All rights reserved.
Upadhyay, Mohita; Sharma, Neha; Vivekanandan, Perumal
2014-01-01
Differences in the relative abundance of dinucleotides, if any may provide important clues on host-driven evolution of viruses. We studied dinucleotide frequencies of large DNA viruses infecting vertebrates (n = 105; viruses infecting mammals = 99; viruses infecting aves = 6; viruses infecting reptiles = 1) and invertebrates (n = 88; viruses infecting insects = 84; viruses infecting crustaceans = 4). We have identified systematic depletion of CpT(ApG) dinucleotides and over-representation of CpG dinucleotides as the unique genomic signature of large DNA viruses infecting invertebrates. Detailed investigation of this unique genomic signature suggests the existence of invertebrate host-induced pressures specifically targeting CpT(ApG) and CpG dinucleotides. The depletion of CpT dinucleotides among large DNA viruses infecting invertebrates is at least in part, explained by non-canonical DNA methylation by the infected host. Our findings highlight the role of invertebrate host-related factors in shaping virus evolution and they also provide the necessary framework for future studies on evolution, epigenetics and molecular biology of viruses infecting this group of hosts.
Evolution of deformation in neutron-rich Ba isotopes up to A =150
NASA Astrophysics Data System (ADS)
Licǎ, R.; Benzoni, G.; Rodríguez, T. R.; Borge, M. J. G.; Fraile, L. M.; Mach, H.; Morales, A. I.; Madurga, M.; Sotty, C. O.; Vedia, V.; De Witte, H.; Benito, J.; Bernard, R. N.; Berry, T.; Bracco, A.; Camera, F.; Ceruti, S.; Charviakova, V.; Cieplicka-Oryńczak, N.; Costache, C.; Crespi, F. C. L.; Creswell, J.; Fernandez-Martínez, G.; Fynbo, H.; Greenlees, P. T.; Homm, I.; Huyse, M.; Jolie, J.; Karayonchev, V.; Köster, U.; Konki, J.; Kröll, T.; Kurcewicz, J.; Kurtukian-Nieto, T.; Lazarus, I.; Lund, M. V.; Mǎrginean, N.; Mǎrginean, R.; Mihai, C.; Mihai, R. E.; Negret, A.; Orduz, A.; Patyk, Z.; Pascu, S.; Pucknell, V.; Rahkila, P.; Rapisarda, E.; Regis, J. M.; Robledo, L. M.; Rotaru, F.; Saed-Samii, N.; Sánchez-Tembleque, V.; Stanoiu, M.; Tengblad, O.; Thuerauf, M.; Turturica, A.; Van Duppen, P.; Warr, N.; IDS Collaboration
2018-02-01
The occurrence of octupolar shapes in the Ba isotopic chain was recently established experimentally up to N =90 . To further extend the systematics, the evolution of shapes in the most neutron-rich members of the Z =56 isotopic chain accessible at present, Ba,150148, has been studied via β decay at the ISOLDE Decay Station. This paper reports on the first measurement of the positive- and negative-parity low-spin excited states of 150Ba and presents an extension of the β -decay scheme of 148Cs. Employing the fast timing technique, half-lives for the 21+ level in both nuclei have been determined, resulting in T1 /2=1.51 (1 ) ns for 148Ba and T1 /2=3.4 (2 ) ns for 150Ba. The systematics of low-spin states, together with the experimental determination of the B (E 2 :2+→0+) transition probabilities, indicate an increasing collectivity in Ba-150148, towards prolate deformed shapes. The experimental data are compared to symmetry conserving configuration mixing (SCCM) calculations, confirming an evolution of increasingly quadrupole deformed shapes with a definite octupolar character.
Pavenski, Katerina; Stanworth, Simon; Fung, Mark; Wood, Erica M; Pink, Joanne; Murphy, Michael F; Hume, Heather; Nahirniak, Susan; Webert, Kathryn E; Tanael, Susano; Landry, Denise; Shehata, Nadine
2018-06-01
Many transfusion guidelines are available, but little appraisal of their quality has been undertaken. The quality of guidelines may potentially influence adoption. Our aim was to determine the quality of evidence-based transfusion guidelines (EBG) for red cells and plasma, using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument, and assess duplication and consistency of recommendations. MEDLINE and EMBASE were systematically searched for EBG from 2005 to June 3, 2016. Citations were reviewed for inclusion in duplicate. A guideline was included if it had a specified clinical question, described a systematic search strategy, included critical appraisal of the literature and a description of how recommendations were developed. Four to six physicians used AGREE II to appraise each guideline. Median and scaled scores were calculated, with each item scored on a scale of one to seven, seven representing the highest score. Of 6174 citations, 30 guidelines met inclusion criteria. Twenty six guidelines had recommendations for red cells and 18 included recommendations for plasma use. The median score, the scaled score and the interquartile range of the scaled score were: scope and purpose: median score 5, scaled score 60%, IQR (49-74%); stakeholder involvement 4, 43%, (33-49%); rigor of development 4, 41%, (19-59%); clarity of presentation 5, 69%, (52-81%); applicability 1, 16%, (9-23%); editorial independence 3, 43%, (20-58%). Sixteen guidelines were evaluated to have a scaled domain score of 50% or less. Variations in recommendations were found for the use of hemoglobin triggers for red cell transfusion in patients with acute coronary syndromes and for plasma use for patients with bleeding. Our findings document, limited rigor in guideline development and duplication and inconsistencies in recommendations for the same topic. The process of developing guidelines for red cells and plasma transfusion can be enhanced to improve implementation. Copyright © 2018 Elsevier Inc. All rights reserved.
Primary B cell lymphoma of the tongue base: a case report
Bechir, Achour; Asma, Achour; Haifa, Regaieg; Nesrine, Abdessayed; Yosra, Ben Youssef; Badreddine, Sriha; Abderrahim, Khelif
2016-01-01
Primary non-Hodgkin’s lymphoma’s of the tongue is very rare and accounts for 1% of all malignant tumor of the oral cavity. Clinical features are non-specific ulcerative lesions that do not heal. In the literature, the majority of cases are diffuse large B cell type however, T cell phenotype also may occur. We describe a 77 years old man, who presented with an ulcerative mass in the left margin of the tongue the diagnosis diffuse large B cell lymphoma was confirmed. The patient is actually on treatment R-mini CEOP and has favorable evolution. PMID:28292136
Gini, Beatrice; Mischel, Paul S
2014-08-01
Single-cell sequencing approaches are needed to characterize the genomic diversity of complex tumors, shedding light on their evolutionary paths and potentially suggesting more effective therapies. In this issue of Cancer Discovery, Francis and colleagues develop a novel integrative approach to identify distinct tumor subpopulations based on joint detection of clonal and subclonal events from bulk tumor and single-nucleus whole-genome sequencing, allowing them to infer a subclonal architecture. Surprisingly, the authors identify convergent evolution of multiple, mutually exclusive, independent EGFR gain-of-function variants in a single tumor. This study demonstrates the value of integrative single-cell genomics and highlights the biologic primacy of EGFR as an actionable target in glioblastoma. ©2014 American Association for Cancer Research.
Probing galaxy growth through metallicity scaling relations over the past 12 Gyr of cosmic history
NASA Astrophysics Data System (ADS)
Sanders, Ryan; MOSDEF team
2018-01-01
A primary goal of galaxy evolution studies is to understand the processes governing the growth of the baryonic content of galaxies over cosmic history. Observations of galaxy metallicity scaling relations and their evolution with redshift, in combination with chemical evolution models, provide unique insight into the interplay between star formation, gas accretion, and feedback/outflows. I present measurements of the stellar mass-gas phase metallicity relation and its evolution over the past 12 Gyr from z~0 to z~3.5, utilizing data from the Mosfire Deep Evolution Field survey that uniquely provides rest-frame optical spectra of >1000 uniformly-selected galaxies at z=1.3-3.8. We find evolution towards lower metallicity at fixed stellar mass with increasing redshift that is consistent with current cosmological simulations including chemical evolution, with a large evolution of ~0.3 dex from z~0 to z~2.5 and minor evolution of <0.1 dex from z~2.5 to z~3.5. We unambiguously confirm the existence of star-formation rate dependence of the mass-metallicity relation at high redshift for the first time. A clear view of cosmic chemical evolution requires accounting for systematic biases in galaxy metallicity measurements at both low and high redshifts. We use a set of empirically-based models to correct for diffuse ionized gas contamination that biases metallicity estimates from z~0 global galaxy spectra. Evolving properties of ionized gas such as electron density, ionization parameter, hardness of the ionizing spectrum, and chemical abundance patterns may render locally-calibrated metallicity estimators unreliable at high redshifts. Using strong-line ratios alone, it is extremely difficult to break degenerate solutions between pure metallicity evolution and additional evolution of the ionization parameter and/or shape of the ionizing spectrum. Temperature-sensitive auroral-line measurements provide a way to directly and independently measure metallicities, breaking these degeneracies. We present measurements of auroral [OIII]4363 and direct-method metallicities at z>2, and discuss the potential of current and next-generation observational facilities to obtain statistical auroral-line samples at high redshifts.
Fundamental Investigations and Rational Design of Durable High-Performance SOFC Cathodes
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, Yu; Ding, Dong; Wei, Tao
The main objective of this project is to unravel the degradation mechanism of LSCF cathodes under realistic operating conditions with different types of contaminants, aiming towards the rational design of cathodes with high-performance and enhanced durability by combining a porous backbone (such as LSCF) with a thin catalyst coating. The mechanistic understanding will help us to optimize the composition and morphology of the catalyst layer and microstructure of the LSCF backbone for better performance and durability. More specifically, the technical objectives include: (1) to unravel the degradation mechanism of LSCF cathodes under realistic operating conditions with different types of contaminantsmore » using in situ and ex situ measurements performed on specially-designed cathodes; (2) to examine the microstructural and compositional evolution of LSCF cathodes as well as the cathode/electrolyte interfaces under realistic operating conditions; (3) to correlate the fuel cell performance instability and degradation with the microstructural and morphological evolution and surface chemistry change of the cathode under realistic operating conditions; (4) to explore new catalyst materials and electrode structures to enhance the stability of the LSCF cathode under realistic operating conditions; and (5) to validate the long term stability of the modified LSCF cathode in commercially available cells under realistic operating conditions. We have systematically evaluated LSCF cathodes in symmetrical cells and anode supported cells under realistic conditions with different types of contaminants such as humidity, CO 2, and Cr. Electrochemical models for the design of test cells and understanding of mechanisms have been developed for the exploration of fundamental properties of electrode materials. It is demonstrated that the activity and stability of LSCF cathodes can be degraded by the introduction of contaminants. The microstructural and compositional evolution of LSCF cathodes as well as the cathode/electrolyte interfaces under realistic operating conditions has been studied. It is found that SrO readily segregated/enriched on the LSCF surface. More severe contamination conditions cause more SrO on surface. Novel catalyst coatings through particle depositions (PrOx) or continuous thin films (PNM) were successfully developed to improve the activity and stability of LSCF cathodes. Finally, we have demonstrated enhanced activity and stability of LSCF cathodes over longer periods of time in homemade and commercially available cells by an optimized PNM (dense film and particles) infiltration process, under clean air and realistic operating conditions (3% H 2O, 5% CO 2 and direct Crofer contact). Both performance and durability of single cells with PNM coating has been enhanced compared with those without coating. Raman analysis of cathodes surface indicated that the intensity of SrCrO 4 was significantly decreased.« less
Brödel, Andreas K; Jaramillo, Alfonso; Isalan, Mark
2017-09-01
Directed evolution is a powerful tool to improve the characteristics of biomolecules. Here we present a protocol for the intracellular evolution of proteins with distinct differences and advantages in comparison with established techniques. These include the ability to select for a particular function from a library of protein variants inside cells, minimizing undesired coevolution and propagation of nonfunctional library members, as well as allowing positive and negative selection logics using basally active promoters. A typical evolution experiment comprises the following stages: (i) preparation of a combinatorial M13 phagemid (PM) library expressing variants of the gene of interest (GOI) and preparation of the Escherichia coli host cells; (ii) multiple rounds of an intracellular selection process toward a desired activity; and (iii) the characterization of the evolved target proteins. The system has been developed for the selection of new orthogonal transcription factors (TFs) but is capable of evolving any gene-or gene circuit function-that can be linked to conditional M13 phage replication. Here we demonstrate our approach using as an example the directed evolution of the bacteriophage λ cI TF against two synthetic bidirectional promoters. The evolved TF variants enable simultaneous activation and repression against their engineered promoters and do not cross-react with the wild-type promoter, thus ensuring orthogonality. This protocol requires no special equipment, allowing synthetic biologists and general users to evolve improved biomolecules within ∼7 weeks.
NASA Astrophysics Data System (ADS)
Levo, E.; Granberg, F.; Fridlund, C.; Nordlund, K.; Djurabekova, F.
2017-07-01
Single-phase multicomponent alloys of equal atomic concentrations ("equiatomic") have proven to exhibit promising mechanical and corrosion resistance properties, that are sought after in materials intended for use in hazardous environments like next-generation nuclear reactors. In this article, we investigate the damage production and dislocation mobility by simulating irradiation of elemental Ni and the alloys NiCo, NiCoCr, NiCoFe and NiFe, to assess the effect of elemental composition. We compare the defect production and the evolution of dislocation networks in the simulation cells of two different sizes, for all five studied materials. We find that the trends in defect evolution are in good agreement between the different cell sizes. The damage is generally reduced with increased alloy complexity, and the dislocation evolution is specific to each material, depending on its complexity. We show that increasing complexity of the alloys does not always lead to decreased susceptibility to damage accumulation under irradiation. We show that, for instance, the NiCo alloy behaves very similarly to Ni, while presence of Fe or Cr in the alloy even as a third component reduces the saturated level of damage substantially. Moreover, we linked the defect evolution with the dislocation transformations in the alloys. Sudden drops in defect number and large defect fluctuations from the continuous irradiation can be explained from the dislocation activity.
Carbon-based electrocatalysts for advanced energy conversion and storage
Zhang, Jintao; Xia, Zhenhai; Dai, Liming
2015-01-01
Oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) play curial roles in electrochemical energy conversion and storage, including fuel cells and metal-air batteries. Having rich multidimensional nanoarchitectures [for example, zero-dimensional (0D) fullerenes, 1D carbon nanotubes, 2D graphene, and 3D graphite] with tunable electronic and surface characteristics, various carbon nanomaterials have been demonstrated to act as efficient metal-free electrocatalysts for ORR and OER in fuel cells and batteries. We present a critical review on the recent advances in carbon-based metal-free catalysts for fuel cells and metal-air batteries, and discuss the perspectives and challenges in this rapidly developing field of practical significance. PMID:26601241
Cobey, Sarah; Wilson, Patrick; Matsen, Frederick A.
2015-01-01
The B-cell immune response is a remarkable evolutionary system found in jawed vertebrates. B-cell receptors, the membrane-bound form of antibodies, are capable of evolving high affinity to almost any foreign protein. High germline diversity and rapid evolution upon encounter with antigen explain the general adaptability of B-cell populations, but the dynamics of repertoires are less well understood. These dynamics are scientifically and clinically important. After highlighting the remarkable characteristics of naive and experienced B-cell repertoires, especially biased usage of genes encoding the B-cell receptors, we contrast methods of sequence analysis and their attempts to explain patterns of B-cell evolution. These phylogenetic approaches are currently unlinked to explicit models of B-cell competition, which analyse repertoire evolution at the level of phenotype, the affinities and specificities to particular antigenic sites. The models, in turn, suggest how chance, infection history and other factors contribute to different patterns of immunodominance and protection between people. Challenges in rational vaccine design, specifically vaccines to induce broadly neutralizing antibodies to HIV, underscore critical gaps in our understanding of B cells' evolutionary and ecological dynamics. PMID:26194749
Bertaux, François; Stoma, Szymon; Drasdo, Dirk; Batt, Gregory
2014-01-01
Isogenic cells sensing identical external signals can take markedly different decisions. Such decisions often correlate with pre-existing cell-to-cell differences in protein levels. When not neglected in signal transduction models, these differences are accounted for in a static manner, by assuming randomly distributed initial protein levels. However, this approach ignores the a priori non-trivial interplay between signal transduction and the source of this cell-to-cell variability: temporal fluctuations of protein levels in individual cells, driven by noisy synthesis and degradation. Thus, modeling protein fluctuations, rather than their consequences on the initial population heterogeneity, would set the quantitative analysis of signal transduction on firmer grounds. Adopting this dynamical view on cell-to-cell differences amounts to recast extrinsic variability into intrinsic noise. Here, we propose a generic approach to merge, in a systematic and principled manner, signal transduction models with stochastic protein turnover models. When applied to an established kinetic model of TRAIL-induced apoptosis, our approach markedly increased model prediction capabilities. One obtains a mechanistic explanation of yet-unexplained observations on fractional killing and non-trivial robust predictions of the temporal evolution of cell resistance to TRAIL in HeLa cells. Our results provide an alternative explanation to survival via induction of survival pathways since no TRAIL-induced regulations are needed and suggest that short-lived anti-apoptotic protein Mcl1 exhibit large and rare fluctuations. More generally, our results highlight the importance of accounting for stochastic protein turnover to quantitatively understand signal transduction over extended durations, and imply that fluctuations of short-lived proteins deserve particular attention. PMID:25340343
The Value of Circulating Biomarkers in Bicuspid Aortic Valve-Associated Aortopathy.
Naito, Shiho; Hillebrand, Mathias; Bernhardt, Alexander Martin Justus; Jagodzinski, Annika; Conradi, Lenard; Detter, Christian; Sydow, Karsten; Reichenspurner, Hermann; Kodolitsch, Yskert von; Girdauskas, Evaldas
2018-06-01
Traditional risk stratification model of bicuspid aortic valve (BAV) aortopathy is based on measurement of maximal cross-sectional aortic diameter, definition of proximal aortic shape, and aortic stiffness/elasticity parameters. However, conventional imaging-based criteria are unable to provide reliable information regarding the risk stratification in BAV aortopathy, especially considering the heterogeneous nature of BAV disease. Given those limitations of conventional imaging, there is a growing clinical interest to use circulating biomarkers in the screening process for thoracic aortic aneurysms as well as in the risk-assessment algorithms. We aimed to systematically review currently available biomarkers, which may be of value to predict the natural evolution of aortopathy in individuals with BAV. Georg Thieme Verlag KG Stuttgart · New York.
Experimental Evolution Reveals Favored Adaptive Routes to Cell Aggregation in Yeast.
Hope, Elyse A; Amorosi, Clara J; Miller, Aaron W; Dang, Kolena; Heil, Caiti Smukowski; Dunham, Maitreya J
2017-06-01
Yeast flocculation is a community-building cell aggregation trait that is an important mechanism of stress resistance and a useful phenotype for brewers; however, it is also a nuisance in many industrial processes, in clinical settings, and in the laboratory. Chemostat-based evolution experiments are impaired by inadvertent selection for aggregation, which we observe in 35% of populations. These populations provide a testing ground for understanding the breadth of genetic mechanisms Saccharomyces cerevisiae uses to flocculate, and which of those mechanisms provide the biggest adaptive advantages. In this study, we employed experimental evolution as a tool to ask whether one or many routes to flocculation are favored, and to engineer a strain with reduced flocculation potential. Using a combination of whole genome sequencing and bulk segregant analysis, we identified causal mutations in 23 independent clones that had evolved cell aggregation during hundreds of generations of chemostat growth. In 12 of those clones, we identified a transposable element insertion in the promoter region of known flocculation gene FLO1 , and, in an additional five clones, we recovered loss-of-function mutations in transcriptional repressor TUP1 , which regulates FLO1 and other related genes. Other causal mutations were found in genes that have not been previously connected to flocculation. Evolving a flo1 deletion strain revealed that this single deletion reduces flocculation occurrences to 3%, and demonstrated the efficacy of using experimental evolution as a tool to identify and eliminate the primary adaptive routes for undesirable traits. Copyright © 2017 Hope et al.
Experimental Evolution Reveals Favored Adaptive Routes to Cell Aggregation in Yeast
Hope, Elyse A.; Amorosi, Clara J.; Miller, Aaron W.; Dang, Kolena; Heil, Caiti Smukowski; Dunham, Maitreya J.
2017-01-01
Yeast flocculation is a community-building cell aggregation trait that is an important mechanism of stress resistance and a useful phenotype for brewers; however, it is also a nuisance in many industrial processes, in clinical settings, and in the laboratory. Chemostat-based evolution experiments are impaired by inadvertent selection for aggregation, which we observe in 35% of populations. These populations provide a testing ground for understanding the breadth of genetic mechanisms Saccharomyces cerevisiae uses to flocculate, and which of those mechanisms provide the biggest adaptive advantages. In this study, we employed experimental evolution as a tool to ask whether one or many routes to flocculation are favored, and to engineer a strain with reduced flocculation potential. Using a combination of whole genome sequencing and bulk segregant analysis, we identified causal mutations in 23 independent clones that had evolved cell aggregation during hundreds of generations of chemostat growth. In 12 of those clones, we identified a transposable element insertion in the promoter region of known flocculation gene FLO1, and, in an additional five clones, we recovered loss-of-function mutations in transcriptional repressor TUP1, which regulates FLO1 and other related genes. Other causal mutations were found in genes that have not been previously connected to flocculation. Evolving a flo1 deletion strain revealed that this single deletion reduces flocculation occurrences to 3%, and demonstrated the efficacy of using experimental evolution as a tool to identify and eliminate the primary adaptive routes for undesirable traits. PMID:28450459
Sawada, Hitoshi; Satoh, Noriyuki
2016-01-01
Despite the importance of stony corals in many research fields related to global issues, such as marine ecology, climate change, paleoclimatogy, and metazoan evolution, very little is known about the evolutionary origin of coral skeleton formation. In order to investigate the evolution of coral biomineralization, we have identified skeletal organic matrix proteins (SOMPs) in the skeletal proteome of the scleractinian coral, Acropora digitifera, for which large genomic and transcriptomic datasets are available. Scrupulous gene annotation was conducted based on comparisons of functional domain structures among metazoans. We found that SOMPs include not only coral-specific proteins, but also protein families that are widely conserved among cnidarians and other metazoans. We also identified several conserved transmembrane proteins in the skeletal proteome. Gene expression analysis revealed that expression of these conserved genes continues throughout development. Therefore, these genes are involved not only skeleton formation, but also in basic cellular functions, such as cell-cell interaction and signaling. On the other hand, genes encoding coral-specific proteins, including extracellular matrix domain-containing proteins, galaxins, and acidic proteins, were prominently expressed in post-settlement stages, indicating their role in skeleton formation. Taken together, the process of coral skeleton formation is hypothesized as: 1) formation of initial extracellular matrix between epithelial cells and substrate, employing pre-existing transmembrane proteins; 2) additional extracellular matrix formation using novel proteins that have emerged by domain shuffling and rapid molecular evolution and; 3) calcification controlled by coral-specific SOMPs. PMID:27253604
Liu, Lin; Nardo, David; Li, Eric; Wang, Gary P
2016-03-13
CD4 T-cell depletion from HIV infection leads to a global decline in anti-hepatitis C virus (HCV) envelope neutralizing antibody (nAb) response, which may play a role in accelerating liver fibrosis. An increase in anti-HCV nAb titers has been reported during antiretroviral therapy (ART) but its impact on HCV remains poorly understood. The objective of this study is to determine the effects of ART on long-term HCV evolution. We examined HCV quasispecies structure and long-term evolution in HIV/HCV coinfected patients with ART-induced CD4 T-cell recovery, and compared with patients with CD4 T-cell depletion from delayed ART. We applied a single-variant sequencing (SVS) method to construct authentic viral quasispecies and compared sequence evolution in HCV envelope, the primary target for humoral immune responses, and NS3, a target for cellular immunity, between the two cohorts. The SVS method corrected biases known to skew the proportions of viral variants, revealing authentic HCV quasispeices structures. We observed higher rates of HCV envelope sequence evolution in patients with ART-induced CD4 T-cell recovery, compared with patients with CD4 T-cell depletion from delayed ART (P = 0.03). Evolutionary rates for NS3 were considerably lower than the rates for envelope (P < 0.01), with no significant difference observed between the two groups. ART-induced CD4 T-cell recovery results in rapid sequence evolution in HCV envelope, but not in NS3. These results suggest that suppressive ART disproportionally enhances HCV-specific humoral responses more than cellular responses, resulting in rapid sequence evolution in HCV envelope but not NS3.
Analysis and IbM simulation of the stages in bacterial lag phase: basis for an updated definition.
Prats, Clara; Giró, Antoni; Ferrer, Jordi; López, Daniel; Vives-Rego, Josep
2008-05-07
The lag phase is the initial phase of a culture that precedes exponential growth and occurs when the conditions of the culture medium differ from the pre-inoculation conditions. It is usually defined by means of cell density because the number of individuals remains approximately constant or slowly increases, and it is quantified with the lag parameter lambda. The lag phase has been studied through mathematical modelling and by means of specific experiments. In recent years, Individual-based Modelling (IbM) has provided helpful insights into lag phase studies. In this paper, the definition of lag phase is thoroughly examined. Evolution of the total biomass and the total number of bacteria during lag phase is tackled separately. The lag phase lasts until the culture reaches a maximum growth rate both in biomass and cell density. Once in the exponential phase, both rates are constant over time and equal to each other. Both evolutions are split into an initial phase and a transition phase, according to their growth rates. A population-level mathematical model is presented to describe the transitional phase in cell density. INDividual DIScrete SIMulation (INDISIM) is used to check the outcomes of this analysis. Simulations allow the separate study of the evolution of cell density and total biomass in a batch culture, they provide a depiction of different observed cases in lag evolution at the individual-cell level, and are used to test the population-level model. The results show that the geometrical lag parameter lambda is not appropriate as a universal definition for the lag phase. Moreover, the lag phase cannot be characterized by a single parameter. For the studied cases, the lag phases of both the total biomass and the population are required to fully characterize the evolution of bacterial cultures. The results presented prove once more that the lag phase is a complex process that requires a more complete definition. This will be possible only after the phenomena governing the population dynamics at an individual level of description, and occurring during the lag and exponential growth phases, are well understood.
Intraclass Evolution and Classification of the Colpodea (Ciliophora)
FOISSNER, WILHELM; STOECK, THORSTEN; AGATHA, SABINE; DUNTHORN, MICAH
2012-01-01
Using nine new taxa and statistical inferences based on morphological and molecular data, we analyze the evolution within the class Colpodea. The molecular and cladistic analyses show four well-supported clades: platyophryids, bursariomorphids, cyrtolophosidids, and colpodids. There is a widespread occurrence of homoplasies, affecting even conspicuous morphological characteristics, e.g. the inclusion of the micronucleus in the perinuclear space of the macronucleus. The most distinct changes in the morphological classification are the lack of a basal divergence into two subclasses and the split of the cyrtolophosidids into two main clades, differing mainly by the presence vs. absence of an oral cavity. The most complex clade is that of the colpodids. We partially reconcile the morphological and molecular data using evolutionary systematics, providing a scenario in which the colpodids evolved from a Bardeliella-like ancestor and the genus Colpoda performed an intense adaptive radiation, giving rise to three main clades: Colpodina n. subord., Grossglockneriina, and Bryophryina. Three new taxa are established: Colpodina n. subord., Tillinidae n. fam., and Ottowphryidae n. fam. Colpodean evolution and classification are far from being understood because sequences are lacking for most species and half of their diversity is possibly undescribed. PMID:21762424
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hu, Shenyang Y.; Setyawan, Wahyu; Van Ginhoven, Renee M.
2014-02-20
Density functional theory (DFT) is used to calculate the thermodynamic and kinetic properties of transmutant Mg in 3C-SiC due to high-energy neutron irradiation associated with the fusion nuclear environment. The formation and binding energies of intrinsic defects, Mg-related defects, and clusters in 3C-SiC are systematically calculated. The minimum energy paths and activation energies during point defect migration and small cluster evolution are studied using a generalized solid-state elastic band (G-SSNEB) method with DFT energy calculations. Stable defect structures and possible defect migration mechanisms are identified. The evolution of binding energies during Mg2Si formation demonstrates that the formation of Mg2Si needsmore » to overcome a critical nucleus size and nucleation barrier. It is also found that a compressive stress field exists around the Mg2Si nucleus. These data are important inputs in meso- and macro-scale modeling and experiments to understand and predict the impact of Mg on phase stability, microstructure evolution, and performance of SiC and SiC-based materials during long-term neutron exposures.« less
Evolution of cooperation among tumor cells.
Axelrod, Robert; Axelrod, David E; Pienta, Kenneth J
2006-09-05
The evolution of cooperation has a well established theoretical framework based on game theory. This approach has made valuable contributions to a wide variety of disciplines, including political science, economics, and evolutionary biology. Existing cancer theory suggests that individual clones of cancer cells evolve independently from one another, acquiring all of the genetic traits or hallmarks necessary to form a malignant tumor. It is also now recognized that tumors are heterotypic, with cancer cells interacting with normal stromal cells within the tissue microenvironment, including endothelial, stromal, and nerve cells. This tumor cell-stromal cell interaction in itself is a form of commensalism, because it has been demonstrated that these nonmalignant cells support and even enable tumor growth. Here, we add to this theory by regarding tumor cells as game players whose interactions help to determine their Darwinian fitness. We marshal evidence that tumor cells overcome certain host defenses by means of diffusible products. Our original contribution is to raise the possibility that two nearby cells can protect each other from a set of host defenses that neither could survive alone. Cooperation can evolve as by-product mutualism among genetically diverse tumor cells. Our hypothesis supplements, but does not supplant, the traditional view of carcinogenesis in which one clonal population of cells develops all of the necessary genetic traits independently to form a tumor. Cooperation through the sharing of diffusible products raises new questions about tumorigenesis and has implications for understanding observed phenomena, designing new experiments, and developing new therapeutic approaches.
Strobl, Frederic; Schmitz, Alexander; Stelzer, Ernst H K
2017-06-01
Light-sheet-based fluorescence microscopy features optical sectioning in the excitation process. This reduces phototoxicity and photobleaching by up to four orders of magnitude compared with that caused by confocal fluorescence microscopy, simplifies segmentation and quantification for three-dimensional cell biology, and supports the transition from on-demand to systematic data acquisition in developmental biology applications.
Reweaving the Tapestry: a Supertree of Birds
Davis, Katie E; Page, Roderic D. M.
2014-01-01
Our knowledge of the avian tree of life remains uncertain, particularly at deeper levels due to the rapid diversification early in their evolutionary history. They are the most abundant land vertebrate on the planet and have been of great historical interest to systematists. Birds are also economically and ecologically important and as a result are intensively studied, yet despite their importance and interest to humans around 13% of taxa currently on the endangered species list perhaps as a result of human activity. Despite all this no comprehensive phylogeny that includes both extinct and extant species currently exists. Here we present a species-level supertree, constructed using the Matrix Representation with Parsimony method, of Aves containing approximately two thirds of all species from nearly 1000 source phylogenies with a broad taxonomic coverage. The source data for the tree were collected and processed according to a strict protocol to ensure robust and accurate data handling. The resulting tree topology is largely consistent with molecular hypotheses of avian phylogeny. We identify areas that are in broad agreement with current views on avian systematics and also those that require further work. We also highlight the need for leaf-based support measures to enable the identification of rogue taxa in supertrees. This is a first attempt at a supertree of both extinct and extant birds, it is not intended to be utilised in an overhaul of avian systematics or as a basis for taxonomic re-classification but provides a strong basis on which to base further studies on macroevolution, conservation, biodiversity, comparative biology and character evolution, in particular the inclusion of fossils will allow the study of bird evolution and diversification throughout deep time. PMID:24944845
Study on component interface evolution of a solid oxide fuel cell stack after long term operation
NASA Astrophysics Data System (ADS)
Yang, Jiajun; Huang, Wei; Wang, Xiaochun; Li, Jun; Yan, Dong; Pu, Jian; Chi, Bo; Li, Jian
2018-05-01
A 5-cell solid oxide fuel cell (SOFC) stack with external manifold structure is assembled and underwent a durability test with an output of 250 W for nearly 4400 h when current density and operating temperature are 355 mA/cm2 and 750 °C. Cells used in the stack are anode-supported cells (ASC) with yttria-stabilized zirconia (YSZ) electrolytes, Ni/YSZ hydrogen electrodes, and YSZ based composite cathode. The dimension of the cell is 150 × 150 mm (active area: 130 × 130 mm). Ceramic-glass sealant is used in the stack to keep the gas tightness between cells, interconnects and manifolds. Pure hydrogen and dry air are used as fuel and oxidant respectively. The stack has a maximum output of 340 W at 562 mA/cm2 current density at 750 °C. The stack shows a degradation of 1.5% per 1000 h during the test with 2 thermal cycles to room temperature. After the test, the stack was dissembled and examined. The relationship between microstructure changes of interfaces and degradation in the stack are discussed. The microstructure evolution of interfaces between electrode, contact material and current collector are unveiled and their relationship with the degradation is discussed.
Cell-free protein synthesis: the state of the art.
Whittaker, James W
2013-02-01
Cell-free protein synthesis harnesses the synthetic power of biology, programming the ribosomal translational machinery of the cell to create macromolecular products. Like PCR, which uses cellular replication machinery to create a DNA amplifier, cell-free protein synthesis is emerging as a transformative technology with broad applications in protein engineering, biopharmaceutical development, and post-genomic research. By breaking free from the constraints of cell-based systems, it takes the next step towards synthetic biology. Recent advances in reconstituted cell-free protein synthesis (Protein synthesis Using Recombinant Elements expression systems) are creating new opportunities to tailor the reactions for specialized applications including in vitro protein evolution, printing protein microarrays, isotopic labeling, and incorporating nonnatural amino acids.
Distinct Mutations Led to Inactivation of Type 1 Fimbriae Expression in Shigella spp.
Bravo, Verónica; Puhar, Andrea; Sansonetti, Philippe; Parsot, Claude; Toro, Cecilia S.
2015-01-01
Shigella spp. are responsible for bacillary dysentery in humans. The acquisition or the modification of the virulence plasmid encoding factors promoting entry of bacteria into and dissemination within epithelial cells was a critical step in the evolution of these bacteria from their Escherichia coli ancestor(s). Incorporation of genomic islands (GI) and gene inactivation also shaped interactions between these pathogens and their human host. Sequence analysis of the GI inserted next to the leuX tRNA gene in S. boydii, S. dysenteriae, S. flexneri, S. sonnei and enteroinvasive E. coli (EIEC) suggests that this region initially carried the fec, yjhATS and fim gene clusters. The fim cluster encoding type I fimbriae is systematically inactivated in both reference strains and clinical isolates and distinct mutations are responsible for this inactivation in at least three phylogenetic groups. To investigate consequences of the presence of fimbriae on the outcome of the interaction of Shigella with host cells, we used a S. flexneri strain harboring a plasmid encoding the E. coli fim operon. Production of fimbriae by this recombinant strain increased the ability of bacteria to adhere to and enter into epithelial cells and had no effect on their ability to disseminate from cell to cell. The observations that production of type I fimbriae increases invasion of epithelial cells and that independent mutations abolish fimbriae production in Shigella suggest that these mutations correspond to pathoadaptive events. PMID:25811616
Evolution and the complexity of bacteriophages.
Serwer, Philip
2007-03-13
The genomes of both long-genome (> 200 Kb) bacteriophages and long-genome eukaryotic viruses have cellular gene homologs whose selective advantage is not explained. These homologs add genomic and possibly biochemical complexity. Understanding their significance requires a definition of complexity that is more biochemically oriented than past empirically based definitions. Initially, I propose two biochemistry-oriented definitions of complexity: either decreased randomness or increased encoded information that does not serve immediate needs. Then, I make the assumption that these two definitions are equivalent. This assumption and recent data lead to the following four-part hypothesis that explains the presence of cellular gene homologs in long bacteriophage genomes and also provides a pathway for complexity increases in prokaryotic cells: (1) Prokaryotes underwent evolutionary increases in biochemical complexity after the eukaryote/prokaryote splits. (2) Some of the complexity increases occurred via multi-step, weak selection that was both protected from strong selection and accelerated by embedding evolving cellular genes in the genomes of bacteriophages and, presumably, also archaeal viruses (first tier selection). (3) The mechanisms for retaining cellular genes in viral genomes evolved under additional, longer-term selection that was stronger (second tier selection). (4) The second tier selection was based on increased access by prokaryotic cells to improved biochemical systems. This access was achieved when DNA transfer moved to prokaryotic cells both the more evolved genes and their more competitive and complex biochemical systems. I propose testing this hypothesis by controlled evolution in microbial communities to (1) determine the effects of deleting individual cellular gene homologs on the growth and evolution of long genome bacteriophages and hosts, (2) find the environmental conditions that select for the presence of cellular gene homologs, (3) determine which, if any, bacteriophage genes were selected for maintaining the homologs and (4) determine the dynamics of homolog evolution. This hypothesis is an explanation of evolutionary leaps in general. If accurate, it will assist both understanding and influencing the evolution of microbes and their communities. Analysis of evolutionary complexity increase for at least prokaryotes should include analysis of genomes of long-genome bacteriophages.
Farag, Mohamed A; Huhman, David V; Lei, Zhentian; Sumner, Lloyd W
2007-02-01
An integrated approach utilizing HPLC-UV-ESI-MS and GC-MS was used for the large-scale and systematic identification of polyphenols in Medicago truncatula root and cell culture. Under optimized conditions, we were able to simultaneously quantify and identify 35 polyphenols including 26 isoflavones, 3 flavones, 2 flavanones, 2 aurones and a chalcone. All identifications were based upon UV spectra, mass spectral characteristics of protonated molecules, tandem mass spectral data, mass measurements obtained using a quadrupole time-of-flight mass spectrometer (QtofMS), and confirmed through the co-characterization of authentic compounds. In specific instances where the stereochemistry of sugar conjugates was uncertain, subsequent enzymatic hydrolysis of the conjugate followed by GC-MS was used to assign the sugar stereochemical configuration. Comparative metabolic profiling of Medicago truncatula root and cell cultures was then performed and revealed significant differences in the isoflavonoid composition of these two tissues.
Pan, Qin; Wang, Qilong; Sun, Xiaoming; Xia, Xianru; Wu, Shimin; Luo, Fengling; Zhang, Xiao-Lian
2014-01-01
The major surface lipoglycan of Mycobacterium tuberculosis (M. tb), mannose-capped lipoarabinomannan (ManLAM), is an immunosuppressive epitope of M. tb. We used systematic evolution of ligands by exponential enrichment (SELEX) to generate an aptamer (ZXL1) that specifically bound to ManLAM from the virulent M. tb strain H37Rv. Aptamer ZXL1 had the highest binding affinity, with an equilibrium dissociation constant (Kd) of 436.3 ± 37.84 nmol/l, and competed with the mannose receptor for binding to ManLAM and M. tb H37Rv. ZXL1 significantly inhibited the ManLAM-induced immunosuppression of CD11c+ dendritic cells (DCs) and enhanced the M. tb antigen–presenting activity of DCs for naive CD4+ Th1 cell activation. More importantly, we demonstrated that injection of aptamer ZXL1 significantly reduced the progression of M. tb H37Rv infections and bacterial loads in lungs of mice and rhesus monkeys. These results suggest that the aptamer ZXL1 is a new potential antimycobacterial agent and tuberculosis vaccine immune adjuvant. PMID:24572295
NASA Astrophysics Data System (ADS)
Mayabadi, A. H.; Waman, V. S.; Kamble, M. M.; Ghosh, S. S.; Gabhale, B. B.; Rondiya, S. R.; Rokade, A. V.; Khadtare, S. S.; Sathe, V. G.; Pathan, H. M.; Gosavi, S. W.; Jadkar, S. R.
2014-02-01
Nanocrystalline thin films of TiO2 were prepared on glass substrates from an aqueous solution of TiCl3 and NH4OH at room temperature using the simple and cost-effective chemical bath deposition (CBD) method. The influence of deposition time on structural, morphological and optical properties was systematically investigated. TiO2 transition from a mixed anatase-rutile phase to a pure rutile phase was revealed by low-angle XRD and Raman spectroscopy. Rutile phase formation was confirmed by FTIR spectroscopy. Scanning electron micrographs revealed that the multigrain structure of as-deposited TiO2 thin films was completely converted into semi-spherical nanoparticles. Optical studies showed that rutile thin films had a high absorption coefficient and a direct bandgap. The optical bandgap decreased slightly (3.29-3.07 eV) with increasing deposition time. The ease of deposition of rutile thin films at low temperature is useful for the fabrication of extremely thin absorber (ETA) solar cells, dye-sensitized solar cells, and gas sensors.
Altered Expression of Polycomb Group Genes in Glioblastoma Multiforme
Li, Gang; Warden, Charles; Zou, Zhaoxia; Neman, Josh; Krueger, Joseph S.; Jain, Alisha; Jandial, Rahul; Chen, Mike
2013-01-01
The Polycomb group (PcG) proteins play a critical role in histone mediated epigenetics which has been implicated in the malignant evolution of glioblastoma multiforme (GBM). By systematically interrogating The Cancer Genome Atlas (TCGA), we discovered widespread aberrant expression of the PcG members in GBM samples compared to normal brain. The most striking differences were upregulation of EZH2, PHF19, CBX8 and PHC2 and downregulation of CBX7, CBX6, EZH1 and RYBP. Interestingly, changes in EZH2, PHF19, CBX7, CBX6 and EZH1 occurred progressively as astrocytoma grade increased. We validated the aberrant expression of CBX6, CBX7, CBX8 and EZH2 in GBM cell lines by Western blotting and qRT-PCR, and further the aberrant expression of CBX6 in GBM tissue samples by immunohistochemical staining. To determine if there was functional significance to the diminished CBX6 levels in GBM, CBX6 was overexpressed in GBM cells resulting in decreased proliferative capacity. In conclusion, aberrant expression of PcG proteins in GBMs may play a role in the development or maintenance of the malignancy. PMID:24260522
Altered expression of polycomb group genes in glioblastoma multiforme.
Li, Gang; Warden, Charles; Zou, Zhaoxia; Neman, Josh; Krueger, Joseph S; Jain, Alisha; Jandial, Rahul; Chen, Mike
2013-01-01
The Polycomb group (PcG) proteins play a critical role in histone mediated epigenetics which has been implicated in the malignant evolution of glioblastoma multiforme (GBM). By systematically interrogating The Cancer Genome Atlas (TCGA), we discovered widespread aberrant expression of the PcG members in GBM samples compared to normal brain. The most striking differences were upregulation of EZH2, PHF19, CBX8 and PHC2 and downregulation of CBX7, CBX6, EZH1 and RYBP. Interestingly, changes in EZH2, PHF19, CBX7, CBX6 and EZH1 occurred progressively as astrocytoma grade increased. We validated the aberrant expression of CBX6, CBX7, CBX8 and EZH2 in GBM cell lines by Western blotting and qRT-PCR, and further the aberrant expression of CBX6 in GBM tissue samples by immunohistochemical staining. To determine if there was functional significance to the diminished CBX6 levels in GBM, CBX6 was overexpressed in GBM cells resulting in decreased proliferative capacity. In conclusion, aberrant expression of PcG proteins in GBMs may play a role in the development or maintenance of the malignancy.
Roux, Simon; Hawley, Alyse K.; Torres Beltran, Monica; ...
2014-08-29
Viruses modulate microbial communities and alter ecosystem functions. However, due to cultivation bottlenecks, specific virus–host interaction dynamics remain cryptic. In this study, we examined 127 single-cell amplified genomes (SAGs) from uncultivated SUP05 bacteria isolated from a model marine oxygen minimum zone (OMZ) to identify 69 viral contigs representing five new genera within dsDNA Caudovirales and ssDNA Microviridae. Infection frequencies suggest that ∼1/3 of SUP05 bacteria is viral-infected, with higher infection frequency where oxygen-deficiency was most severe. Observed Microviridae clonality suggests recovery of bloom-terminating viruses, while systematic co-infection between dsDNA and ssDNA viruses posits previously unrecognized cooperation modes. Analyses of 186more » microbial and viral metagenomes revealed that SUP05 viruses persisted for years, but remained endemic to the OMZ. Finally, identification of virus-encoded dissimilatory sulfite reductase suggests SUP05 viruses reprogram their host's energy metabolism. Together, these results demonstrate closely coupled SUP05 virus–host co-evolutionary dynamics with the potential to modulate biogeochemical cycling in climate-critical and expanding OMZs.« less
Engineering modular ester fermentative pathways in Escherichia coli.
Layton, Donovan S; Trinh, Cong T
2014-11-01
Sensation profiles are observed all around us and are made up of many different molecules, such as esters. These profiles can be mimicked in everyday items for their uses in foods, beverages, cosmetics, perfumes, solvents, and biofuels. Here, we developed a systematic 'natural' way to derive these products via fermentative biosynthesis. Each ester fermentative pathway was designed as an exchangeable ester production module for generating two precursors- alcohols and acyl-CoAs that were condensed by an alcohol acyltransferase to produce a combinatorial library of unique esters. As a proof-of-principle, we coupled these ester modules with an engineered, modular, Escherichia coli chassis in a plug-and-play fashion to create microbial cell factories for enhanced anaerobic production of a butyrate ester library. We demonstrated tight coupling between the modular chassis and ester modules for enhanced product biosynthesis, an engineered phenotype useful for directed metabolic pathway evolution. Compared to the wildtype, the engineered cell factories yielded up to 48 fold increase in butyrate ester production from glucose. Copyright © 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.
Wiklander, Oscar P. B.; Bostancioglu, R. Beklem; Welsh, Joshua A.; Zickler, Antje M.; Murke, Florian; Corso, Giulia; Felldin, Ulrika; Hagey, Daniel W.; Evertsson, Björn; Liang, Xiu-Ming; Gustafsson, Manuela O.; Mohammad, Dara K.; Wiek, Constanze; Hanenberg, Helmut; Bremer, Michel; Gupta, Dhanu; Björnstedt, Mikael; Giebel, Bernd; Nordin, Joel Z.; Jones, Jennifer C.; EL Andaloussi, Samir; Görgens, André
2018-01-01
Extracellular vesicles (EVs) can be harvested from cell culture supernatants and from all body fluids. EVs can be conceptually classified based on their size and biogenesis as exosomes and microvesicles. Nowadays, it is however commonly accepted in the field that there is a much higher degree of heterogeneity within these two subgroups than previously thought. For instance, the surface marker profile of EVs is likely dependent on the cell source, the cell’s activation status, and multiple other parameters. Within recent years, several new methods and assays to study EV heterogeneity in terms of surface markers have been described; most of them are being based on flow cytometry. Unfortunately, such methods generally require dedicated instrumentation, are time-consuming and demand extensive operator expertise for sample preparation, acquisition, and data analysis. In this study, we have systematically evaluated and explored the use of a multiplex bead-based flow cytometric assay which is compatible with most standard flow cytometers and facilitates a robust semi-quantitative detection of 37 different potential EV surface markers in one sample simultaneously. First, assay variability, sample stability over time, and dynamic range were assessed together with the limitations of this assay in terms of EV input quantity required for detection of differently abundant surface markers. Next, the potential effects of EV origin, sample preparation, and quality of the EV sample on the assay were evaluated. The findings indicate that this multiplex bead-based assay is generally suitable to detect, quantify, and compare EV surface signatures in various sample types, including unprocessed cell culture supernatants, cell culture-derived EVs isolated by different methods, and biological fluids. Furthermore, the use and limitations of this assay to assess heterogeneities in EV surface signatures was explored by combining different sets of detection antibodies in EV samples derived from different cell lines and subsets of rare cells. Taken together, this validated multiplex bead-based flow cytometric assay allows robust, sensitive, and reproducible detection of EV surface marker expression in various sample types in a semi-quantitative way and will be highly valuable for many researchers in the EV field in different experimental contexts.
Systematic analysis of transcription start sites in avian development.
Lizio, Marina; Deviatiiarov, Ruslan; Nagai, Hiroki; Galan, Laura; Arner, Erik; Itoh, Masayoshi; Lassmann, Timo; Kasukawa, Takeya; Hasegawa, Akira; Ros, Marian A; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R R; Kawaji, Hideya; Gusev, Oleg; Sheng, Guojun
2017-09-01
Cap Analysis of Gene Expression (CAGE) in combination with single-molecule sequencing technology allows precision mapping of transcription start sites (TSSs) and genome-wide capture of promoter activities in differentiated and steady state cell populations. Much less is known about whether TSS profiling can characterize diverse and non-steady state cell populations, such as the approximately 400 transitory and heterogeneous cell types that arise during ontogeny of vertebrate animals. To gain such insight, we used the chick model and performed CAGE-based TSS analysis on embryonic samples covering the full 3-week developmental period. In total, 31,863 robust TSS peaks (>1 tag per million [TPM]) were mapped to the latest chicken genome assembly, of which 34% to 46% were active in any given developmental stage. ZENBU, a web-based, open-source platform, was used for interactive data exploration. TSSs of genes critical for lineage differentiation could be precisely mapped and their activities tracked throughout development, suggesting that non-steady state and heterogeneous cell populations are amenable to CAGE-based transcriptional analysis. Our study also uncovered a large set of extremely stable housekeeping TSSs and many novel stage-specific ones. We furthermore demonstrated that TSS mapping could expedite motif-based promoter analysis for regulatory modules associated with stage-specific and housekeeping genes. Finally, using Brachyury as an example, we provide evidence that precise TSS mapping in combination with Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-on technology enables us, for the first time, to efficiently target endogenous avian genes for transcriptional activation. Taken together, our results represent the first report of genome-wide TSS mapping in birds and the first systematic developmental TSS analysis in any amniote species (birds and mammals). By facilitating promoter-based molecular analysis and genetic manipulation, our work also underscores the value of avian models in unravelling the complex regulatory mechanism of cell lineage specification during amniote development.
Munube, Deogratias; Kasirye, Philip; Mupere, Ezekiel; Jin, Zhezhen; LaRussa, Philip; Idro, Richard; Green, Nancy S.
2018-01-01
Objectives. The prevalence of stroke among children with sickle cell disease (SCD) in sub-Saharan Africa was systematically reviewed. Methods. Comprehensive searches of PubMed, Embase, and Web of Science were performed for articles published between 1980 and 2016 (English or French) reporting stroke prevalence. Using preselected inclusion criteria, titles and abstracts were screened and full-text articles were reviewed. Results. Ten full-text articles met selection criteria. Cross-sectional clinic-based data reported 2.9% to 16.9% stroke prevalence among children with SCD. Using available sickle gene frequencies by country, estimated pediatric mortality, and fixed- and random-effects model, the number of affected individuals is projected as 29 800 (95% confidence interval = 25 571-34 027) and 59 732 (37 004-82 460), respectively. Conclusion. Systematic review enabled the estimation of the number of children with SCD stroke in sub-Saharan Africa. High disease mortality, inaccurate diagnosis, and regional variability of risk hamper more precise estimates. Adopting standardized stroke assessments may provide more accurate determination of numbers affected to inform preventive interventions. PMID:29785408
Marks, Lianna J; Munube, Deogratias; Kasirye, Philip; Mupere, Ezekiel; Jin, Zhezhen; LaRussa, Philip; Idro, Richard; Green, Nancy S
2018-01-01
Objectives . The prevalence of stroke among children with sickle cell disease (SCD) in sub-Saharan Africa was systematically reviewed. Methods . Comprehensive searches of PubMed, Embase, and Web of Science were performed for articles published between 1980 and 2016 (English or French) reporting stroke prevalence. Using preselected inclusion criteria, titles and abstracts were screened and full-text articles were reviewed. Results . Ten full-text articles met selection criteria. Cross-sectional clinic-based data reported 2.9% to 16.9% stroke prevalence among children with SCD. Using available sickle gene frequencies by country, estimated pediatric mortality, and fixed- and random-effects model, the number of affected individuals is projected as 29 800 (95% confidence interval = 25 571-34 027) and 59 732 (37 004-82 460), respectively. Conclusion . Systematic review enabled the estimation of the number of children with SCD stroke in sub-Saharan Africa. High disease mortality, inaccurate diagnosis, and regional variability of risk hamper more precise estimates. Adopting standardized stroke assessments may provide more accurate determination of numbers affected to inform preventive interventions.
Usprech, Jenna; Romero, David A; Amon, Cristina H; Simmons, Craig A
2017-08-01
The physical and chemical properties of a biomaterial integrate with soluble cues in the cell microenvironment to direct cell fate and function. Predictable biomaterial-based control of integrated cell responses has been investigated with two-dimensional (2D) screening platforms, but integrated responses in 3D have largely not been explored systematically. To address this need, we developed a screening platform using polyethylene glycol norbornene (PEG-NB) as a model biomaterial with which the polymer wt% (to control elastic modulus) and adhesion peptide types (RGD, DGEA, YIGSR) and densities could be controlled independently and combinatorially in arrays of 3D hydrogels. We applied this platform and regression modeling to identify combinations of biomaterial and soluble biochemical (TGF-β1) factors that best promoted myofibrogenesis of human mesenchymal stromal cells (hMSCs) in order to inform our understanding of regenerative processes for heart valve tissue engineering. In contrast to 2D culture, our screens revealed that soft hydrogels (low PEG-NB wt%) best promoted spread myofibroblastic cells that expressed high levels of α-smooth muscle actin (α-SMA) and collagen type I. High concentrations of RGD enhanced α-SMA expression in the presence of TGF-β1 and cell spreading regardless of whether TGF-β1 was in the culture medium. Strikingly, combinations of peptides that maximized collagen expression depended on the presence or absence of TGF-β1, indicating that biomaterial properties can modulate MSC response to soluble signals. This combination of a 3D biomaterial array screening platform with statistical modeling is broadly applicable to systematically identify combinations of biomaterial and microenvironmental conditions that optimally guide cell responses. We present a novel screening platform and methodology to model and identify how combinations of biomaterial and microenvironmental conditions guide cell phenotypes in 3D. Our approach to systematically identify complex relationships between microenvironmental cues and cell responses enables greater predictive power over cell fate in conditions with interacting material design factors. We demonstrate that this approach not only predicts that mesenchymal stromal cell (MSC) myofibrogenesis is promoted by soft, porous 3D biomaterials, but also generated new insights which demonstrate how biomaterial properties can differentially modulate MSC response to soluble signals. An additional benefit of the process includes utilizing both parametric and non parametric analyses which can demonstrate dominant significant trends as well as subtle interactions between biochemical and biomaterial cues. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Analytical modeling of the temporal evolution of hot spot temperatures in silicon solar cells
NASA Astrophysics Data System (ADS)
Wasmer, Sven; Rajsrima, Narong; Geisemeyer, Ino; Fertig, Fabian; Greulich, Johannes Michael; Rein, Stefan
2018-03-01
We present an approach to predict the equilibrium temperature of hot spots in crystalline silicon solar cells based on the analysis of their temporal evolution right after turning on a reverse bias. For this end, we derive an analytical expression for the time-dependent heat diffusion of a breakdown channel that is assumed to be cylindrical. We validate this by means of thermography imaging of hot spots right after turning on a reverse bias. The expression allows to be used to extract hot spot powers and radii from short-term measurements, targeting application in inline solar cell characterization. The extracted hot spot powers are validated at the hands of long-term dark lock-in thermography imaging. Using a look-up table of expected equilibrium temperatures determined by numerical and analytical simulations, we utilize the determined hot spot properties to predict the equilibrium temperatures of about 100 industrial aluminum back-surface field solar cells and achieve a high correlation coefficient of 0.86 and a mean absolute error of only 3.3 K.
Assessing the toxicity of Pb- and Sn-based perovskite solar cells in model organism Danio rerio
NASA Astrophysics Data System (ADS)
Babayigit, Aslihan; Duy Thanh, Dinh; Ethirajan, Anitha; Manca, Jean; Muller, Marc; Boyen, Hans-Gerd; Conings, Bert
2016-01-01
Intensive development of organometal halide perovskite solar cells has lead to a dramatic surge in power conversion efficiency up to 20%. Unfortunately, the most efficient perovskite solar cells all contain lead (Pb), which is an unsettling flaw that leads to severe environmental concerns and is therefore a stumbling block envisioning their large-scale application. Aiming for the retention of favorable electro-optical properties, tin (Sn) has been considered the most likely substitute. Preliminary studies have however shown that Sn-based perovskites are highly unstable and, moreover, Sn is also enlisted as a harmful chemical, with similar concerns regarding environment and health. To bring more clarity into the appropriateness of both metals in perovskite solar cells, we provide a case study with systematic comparison regarding the environmental impact of Pb- and Sn-based perovskites, using zebrafish (Danio Rerio) as model organism. Uncovering an unexpected route of intoxication in the form of acidification, it is shown that Sn based perovskite may not be the ideal Pb surrogate.
Assessing the toxicity of Pb- and Sn-based perovskite solar cells in model organism Danio rerio
Babayigit, Aslihan; Duy Thanh, Dinh; Ethirajan, Anitha; Manca, Jean; Muller, Marc; Boyen, Hans-Gerd; Conings, Bert
2016-01-01
Intensive development of organometal halide perovskite solar cells has lead to a dramatic surge in power conversion efficiency up to 20%. Unfortunately, the most efficient perovskite solar cells all contain lead (Pb), which is an unsettling flaw that leads to severe environmental concerns and is therefore a stumbling block envisioning their large-scale application. Aiming for the retention of favorable electro-optical properties, tin (Sn) has been considered the most likely substitute. Preliminary studies have however shown that Sn-based perovskites are highly unstable and, moreover, Sn is also enlisted as a harmful chemical, with similar concerns regarding environment and health. To bring more clarity into the appropriateness of both metals in perovskite solar cells, we provide a case study with systematic comparison regarding the environmental impact of Pb- and Sn-based perovskites, using zebrafish (Danio Rerio) as model organism. Uncovering an unexpected route of intoxication in the form of acidification, it is shown that Sn based perovskite may not be the ideal Pb surrogate. PMID:26759068
Quantization of systems with temporally varying discretization. II. Local evolution moves
NASA Astrophysics Data System (ADS)
Höhn, Philipp A.
2014-10-01
Several quantum gravity approaches and field theory on an evolving lattice involve a discretization changing dynamics generated by evolution moves. Local evolution moves in variational discrete systems (1) are a generalization of the Pachner evolution moves of simplicial gravity models, (2) update only a small subset of the dynamical data, (3) change the number of kinematical and physical degrees of freedom, and (4) generate a dynamical (or canonical) coarse graining or refining of the underlying discretization. To systematically explore such local moves and their implications in the quantum theory, this article suitably expands the quantum formalism for global evolution moves, constructed in Paper I [P. A. Höhn, "Quantization of systems with temporally varying discretization. I. Evolving Hilbert spaces," J. Math. Phys. 55, 083508 (2014); e-print arXiv:1401.6062 [gr-qc
Gao, Min-Rui; Liang, Jin-Xia; Zheng, Ya-Rong; Xu, Yun-Fei; Jiang, Jun; Gao, Qiang; Li, Jun; Yu, Shu-Hong
2015-01-01
The electroreduction of water for sustainable hydrogen production is a critical component of several developing clean-energy technologies, such as water splitting and fuel cells. However, finding a cheap and efficient alternative catalyst to replace currently used platinum-based catalysts is still a prerequisite for the commercialization of these technologies. Here we report a robust and highly active catalyst for hydrogen evolution reaction that is constructed by in situ growth of molybdenum disulfide on the surface of cobalt diselenide. In acidic media, the molybdenum disulfide/cobalt diselenide catalyst exhibits fast hydrogen evolution kinetics with onset potential of −11 mV and Tafel slope of 36 mV per decade, which is the best among the non-noble metal hydrogen evolution catalysts and even approaches to the commercial platinum/carbon catalyst. The high hydrogen evolution activity of molybdenum disulfide/cobalt diselenide hybrid is likely due to the electrocatalytic synergistic effects between hydrogen evolution-active molybdenum disulfide and cobalt diselenide materials and the much increased catalytic sites. PMID:25585911
Ca-Pri a Cellular Automata Phenomenological Research Investigation: Simulation Results
NASA Astrophysics Data System (ADS)
Iannone, G.; Troisi, A.
2013-05-01
Following the introduction of a phenomenological cellular automata (CA) model capable to reproduce city growth and urban sprawl, we develop a toy model simulation considering a realistic framework. The main characteristic of our approach is an evolution algorithm based on inhabitants preferences. The control of grown cells is obtained by means of suitable functions which depend on the initial condition of the simulation. New born urban settlements are achieved by means of a logistic evolution of the urban pattern while urban sprawl is controlled by means of the population evolution function. In order to compare model results with a realistic urban framework we have considered, as the area of study, the island of Capri (Italy) in the Mediterranean Sea. Two different phases of the urban evolution on the island have been taken into account: a new born initial growth as induced by geographic suitability and the simulation of urban spread after 1943 induced by the population evolution after this date.
Monge-Pereira, Esther; Ibañez-Pereda, Jaime; Alguacil-Diego, Isabel M; Serrano, Jose I; Spottorno-Rubio, María P; Molina-Rueda, Francisco
2017-09-01
Brain-computer interface (BCI) systems have been suggested as a promising tool for neurorehabilitation. However, to date, there is a lack of homogeneous findings. Furthermore, no systematic reviews have analyzed the degree of validation of these interventions for upper limb (UL) motor rehabilitation poststroke. The study aims were to compile all available studies that assess an UL intervention based on an electroencephalography (EEG) BCI system in stroke; to analyze the methodological quality of the studies retrieved; and to determine the effects of these interventions on the improvement of motor abilities. TYPE: This was a systematic review. Searches were conducted in PubMed, PEDro, Embase, Cumulative Index to Nursing and Allied Health, Web of Science, and Cochrane Central Register of Controlled Trial from inception to September 30, 2015. This systematic review compiles all available studies that assess UL intervention based on an EEG-BCI system in patients with stroke, analyzing their methodological quality using the Critical Review Form for Quantitative Studies, and determining the grade of recommendation of these interventions for improving motor abilities as established by the Oxford Centre for Evidence-based Medicine. The articles were selected according to the following criteria: studies evaluating an EEG-based BCI intervention; studies including patients with a stroke and hemiplegia, regardless of lesion origin or temporal evolution; interventions using an EEG-based BCI to restore functional abilities of the affected UL, regardless of the interface used or its combination with other therapies; and studies using validated tools to evaluate motor function. After the literature search, 13 articles were included in this review: 4 studies were randomized controlled trials; 1 study was a controlled study; 4 studies were case series studies; and 4 studies were case reports. The methodological quality of the included papers ranged from 6 to 15, and the level of evidence varied from 1b to 5. The articles included in this review involved a total of 141 stroke patients. This systematic review suggests that BCI interventions may be a promising rehabilitation approach in subjects with stroke. II. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Eftimie, Raluca
2015-03-01
One of the main unsolved problems of modern physics is finding a "theory of everything" - a theory that can explain, with the help of mathematics, all physical aspects of the universe. While the laws of physics could explain some aspects of the biology of living systems (e.g., the phenomenological interpretation of movement of cells and animals), there are other aspects specific to biology that cannot be captured by physics models. For example, it is generally accepted that the evolution of a cell-based system is influenced by the activation state of cells (e.g., only activated and functional immune cells can fight diseases); on the other hand, the evolution of an animal-based system can be influenced by the psychological state (e.g., distress) of animals. Therefore, the last 10-20 years have seen also a quest for a "theory of everything"-approach extended to biology, with researchers trying to propose mathematical modelling frameworks that can explain various biological phenomena ranging from ecology to developmental biology and medicine [1,2,6]. The basic idea behind this approach can be found in a few reviews on ecology and cell biology [6,7,9-11], where researchers suggested that due to the parallel between the micro-scale dynamics and the emerging macro-scale phenomena in both cell biology and in ecology, many mathematical methods used for ecological processes could be adapted to cancer modelling [7,9] or to modelling in immunology [11]. However, this approach generally involved the use of different models to describe different biological aspects (e.g., models for cell and animal movement, models for competition between cells or animals, etc.).
Systematic gene tagging using CRISPR/Cas9 in human stem cells to illuminate cell organization.
Roberts, Brock; Haupt, Amanda; Tucker, Andrew; Grancharova, Tanya; Arakaki, Joy; Fuqua, Margaret A; Nelson, Angelique; Hookway, Caroline; Ludmann, Susan A; Mueller, Irina A; Yang, Ruian; Horwitz, Rick; Rafelski, Susanne M; Gunawardane, Ruwanthi N
2017-10-15
We present a CRISPR/Cas9 genome-editing strategy to systematically tag endogenous proteins with fluorescent tags in human induced pluripotent stem cells (hiPSC). To date, we have generated multiple hiPSC lines with monoallelic green fluorescent protein tags labeling 10 proteins representing major cellular structures. The tagged proteins include alpha tubulin, beta actin, desmoplakin, fibrillarin, nuclear lamin B1, nonmuscle myosin heavy chain IIB, paxillin, Sec61 beta, tight junction protein ZO1, and Tom20. Our genome-editing methodology using Cas9/crRNA ribonuclear protein and donor plasmid coelectroporation, followed by fluorescence-based enrichment of edited cells, typically resulted in <0.1-4% homology-directed repair (HDR). Twenty-five percent of clones generated from each edited population were precisely edited. Furthermore, 92% (36/39) of expanded clonal lines displayed robust morphology, genomic stability, expression and localization of the tagged protein to the appropriate subcellular structure, pluripotency-marker expression, and multilineage differentiation. It is our conclusion that, if cell lines are confirmed to harbor an appropriate gene edit, pluripotency, differentiation potential, and genomic stability are typically maintained during the clonal line-generation process. The data described here reveal general trends that emerged from this systematic gene-tagging approach. Final clonal lines corresponding to each of the 10 cellular structures are now available to the research community. © 2017 Roberts, Haupt, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
Contrasting Levels of Molecular Evolution on the Mouse X Chromosome
Larson, Erica L.; Vanderpool, Dan; Keeble, Sara; Zhou, Meng; Sarver, Brice A. J.; Smith, Andrew D.; Dean, Matthew D.; Good, Jeffrey M.
2016-01-01
The mammalian X chromosome has unusual evolutionary dynamics compared to autosomes. Faster-X evolution of spermatogenic protein-coding genes is known to be most pronounced for genes expressed late in spermatogenesis, but it is unclear if these patterns extend to other forms of molecular divergence. We tested for faster-X evolution in mice spanning three different forms of molecular evolution—divergence in protein sequence, gene expression, and DNA methylation—across different developmental stages of spermatogenesis. We used FACS to isolate individual cell populations and then generated cell-specific transcriptome profiles across different stages of spermatogenesis in two subspecies of house mice (Mus musculus), thereby overcoming a fundamental limitation of previous studies on whole tissues. We found faster-X protein evolution at all stages of spermatogenesis and faster-late protein evolution for both X-linked and autosomal genes. In contrast, there was less expression divergence late in spermatogenesis (slower late) on the X chromosome and for autosomal genes expressed primarily in testis (testis-biased). We argue that slower-late expression divergence reflects strong regulatory constraints imposed during this critical stage of sperm development and that these constraints are particularly acute on the tightly regulated sex chromosomes. We also found slower-X DNA methylation divergence based on genome-wide bisulfite sequencing of sperm from two species of mice (M. musculus and M. spretus), although it is unclear whether slower-X DNA methylation reflects development constraints in sperm or other X-linked phenomena. Our study clarifies key differences in patterns of regulatory and protein evolution across spermatogenesis that are likely to have important consequences for mammalian sex chromosome evolution, male fertility, and speciation. PMID:27317678
NASA Astrophysics Data System (ADS)
Yang, Dongrui
Corrosion inhibitors as effective anti-corrosion applications were widely studied and drawn much attention in both academe and industrial area. In this work, a systematic work, including inhibitors selection, anti-corrosion property and characterization, influence on scale formation, testing system design and so on, were reported. The corrosion inhibition performance of four imidazolium ionic liquids in carbon dioxide saturated NaCl solution was investigated by using electrochemical and surface analysis technologies. The four compounds are 1-ethyl-3-methylimidazolium chloride (a), 1-butyl-3-methylimidazolium chloride (b), 1-hexyl-3-methylimidazolium chloride (c), 1-decyl-3-methylimidazolium chloride (d). Under the testing conditions, compound d showed the highest inhibition efficiency and selected as the main object of further study. As a selected representative formula, 1-decyl-3-methylimidazolium chloride was studied in detail about its corrosion inhibition performance on mild steel in carbon dioxide saturated NaCl brine at pH 3.8 and 6.8. Electrochemical and surface analysis techniques were used to characterize the specimen corrosion process during the immersion in the blank and inhibiting solutions. The precorrosion of specimen surface showed significant and different influences on the anti-corrosion property of DMICL at pH 3.8 and 6.8. The corrosion inhibition efficiency (IE) was calculated based on parameters obtained from electrochemical techniques; the achieved IE was higher than 98% at the 25th hour for the steel with a well-polished surface at pH 3.8. The fitting parameters obtained from electrochemical data helped to account for the interfacial changes. As proved in previous research, 1-decyl-3-methylimidazolium chloride could be used as good corrosion inhibitors under certain conditions. However, under other conditions, such chemicals, as well as other species in oil transporting system, could be a factor influencing the evolution of protective surface inorganic layer. In this part, the FeCO3 layer evolution process for API 5L X52 carbon steel in CO2-saturated NaCl brine in the absence and in the presence of 1-decyl-3-methylimidazolium chloride ionic liquid was characterized using electrochemical techniques. Two models were developed to account for the interfacial evolution: the first model considered the balance of positive and negative charges at the interface of the metal and electrolyte in blank solution, while the second one considered the layer coverage and evolution with the imidazolium compound. The corrosion testing system is scientifically and practically critical for corrosion testing and simulations. In this part, a flowing fluid loop cell (FFLC) system was constructed to simulate the corrosion environment in the pipeline. Main content of this work include the construction of the flowing fluid cell loop (FFLC) system, as well as FFLC-based corrosion/anticorrosion tests under simulated acid conditions. Electrochemical Impedance Spectroscopy (EIS) and Linear Polarization Resistance (LPR) were used as prime techniques to quantify and characterize the corrosion behaviors of carbon steel specimen. The Eff vs. Reynolds number (Re) plots for the specimen located in the chamber and in the loop branch were provided.
De Boer, Rob J.; Perelson, Alan S.
2017-09-06
Many HIV-1-infected patients evolve broadly neutralizing antibodies (bnAbs). This evolutionary process typically takes several years and is poorly understood as selection taking place in germinal centers occurs on the basis of antibody affinity. B cells with the highest-affinity receptors tend to acquire the most antigen from the follicular dendritic cell (FDC) network and present the highest density of cognate peptides to follicular helper T (Tfh) cells, which provide survival signals to the B cell. bnAbs are therefore expected to evolve only when the B cell lineage evolving breadth is consistently capturing and presenting more peptides to Tfh cells than othermore » lineages of more specific B cells. Here we develop mathematical models of Tfh cells in germinal centers to explicitly define the mechanisms of selection in this complex evolutionary process. Our results suggest that broadly reactive B cells presenting a high density of peptides bound to major histocompatibility complex class II molecules (pMHC) are readily outcompeted by B cells responding to lineages of HIV-1 that transiently dominate the within host viral population. Conversely, if broadly reactive B cells acquire a large variety of several HIV-1 proteins from the FDC network and present a high diversity of several pMHC, they can be rescued by a large fraction of the Tfh cell repertoire in the germinal center. Under such circumstances the evolution of bnAbs is much more consistent. Increasing either the magnitude of the Tfh cell response or the breadth of the Tfh cell repertoire markedly facilitates the evolution of bnAbs. Because both the magnitude and breadth can be increased by vaccination with several HIV-1 proteins, this calls for experimental testing. Many HIV-infected patients slowly evolve antibodies that can neutralize a large variety of viruses. Such broadly neutralizing antibodies (bnAbs) could in the future become therapeutic agents. bnAbs appear very late, and patients are typically not protected by them. At the moment, we fail to understand why this takes so long and how the immune system selects for broadly neutralizing capacity. Typically, antibodies are selected based on affinity and not on breadth. We developed mathematical models to study two different mechanisms by which the immune system can select for broadly neutralizing capacity. One of these is based upon the repertoire of different follicular helper T (Tfh) cells in germinal centers. In conclusion, we suggest that broadly reactive B cells may interact with a larger fraction of this repertoire and demonstrate that this would select for bnAbs. Intriguingly, this suggests that broadening the Tfh cell repertoire by vaccination may speed up the evolution of bnAbs.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
De Boer, Rob J.; Perelson, Alan S.
Many HIV-1-infected patients evolve broadly neutralizing antibodies (bnAbs). This evolutionary process typically takes several years and is poorly understood as selection taking place in germinal centers occurs on the basis of antibody affinity. B cells with the highest-affinity receptors tend to acquire the most antigen from the follicular dendritic cell (FDC) network and present the highest density of cognate peptides to follicular helper T (Tfh) cells, which provide survival signals to the B cell. bnAbs are therefore expected to evolve only when the B cell lineage evolving breadth is consistently capturing and presenting more peptides to Tfh cells than othermore » lineages of more specific B cells. Here we develop mathematical models of Tfh cells in germinal centers to explicitly define the mechanisms of selection in this complex evolutionary process. Our results suggest that broadly reactive B cells presenting a high density of peptides bound to major histocompatibility complex class II molecules (pMHC) are readily outcompeted by B cells responding to lineages of HIV-1 that transiently dominate the within host viral population. Conversely, if broadly reactive B cells acquire a large variety of several HIV-1 proteins from the FDC network and present a high diversity of several pMHC, they can be rescued by a large fraction of the Tfh cell repertoire in the germinal center. Under such circumstances the evolution of bnAbs is much more consistent. Increasing either the magnitude of the Tfh cell response or the breadth of the Tfh cell repertoire markedly facilitates the evolution of bnAbs. Because both the magnitude and breadth can be increased by vaccination with several HIV-1 proteins, this calls for experimental testing. Many HIV-infected patients slowly evolve antibodies that can neutralize a large variety of viruses. Such broadly neutralizing antibodies (bnAbs) could in the future become therapeutic agents. bnAbs appear very late, and patients are typically not protected by them. At the moment, we fail to understand why this takes so long and how the immune system selects for broadly neutralizing capacity. Typically, antibodies are selected based on affinity and not on breadth. We developed mathematical models to study two different mechanisms by which the immune system can select for broadly neutralizing capacity. One of these is based upon the repertoire of different follicular helper T (Tfh) cells in germinal centers. In conclusion, we suggest that broadly reactive B cells may interact with a larger fraction of this repertoire and demonstrate that this would select for bnAbs. Intriguingly, this suggests that broadening the Tfh cell repertoire by vaccination may speed up the evolution of bnAbs.« less
The Evolution of Quorum Sensing as a Mechanism to Infer Kinship
Schluter, Jonas; Schoech, Armin P.; Foster, Kevin R.; Mitri, Sara
2016-01-01
Bacteria regulate many phenotypes via quorum sensing systems. Quorum sensing is typically thought to evolve because the regulated cooperative phenotypes are only beneficial at certain cell densities. However, quorum sensing systems are also threatened by non-cooperative “cheaters” that may exploit quorum-sensing regulated cooperation, which begs the question of how quorum sensing systems are maintained in nature. Here we study the evolution of quorum sensing using an individual-based model that captures the natural ecology and population structuring of microbial communities. We first recapitulate the two existing observations on quorum sensing evolution: density-dependent benefits favor quorum sensing but competition and cheating will destabilize it. We then model quorum sensing in a dense community like a biofilm, which reveals a novel benefit to quorum sensing that is intrinsically evolutionarily stable. In these communities, competing microbial genotypes gradually segregate over time leading to positive correlation between density and genetic similarity between neighboring cells (relatedness). This enables quorum sensing to track genetic relatedness and ensures that costly cooperative traits are only activated once a cell is safely surrounded by clonemates. We hypothesize that under similar natural conditions, the benefits of quorum sensing will not result from an assessment of density but from the ability to infer kinship. PMID:27120081
Sediment transport by runoff on debris-mantled dryland hillslopes
NASA Astrophysics Data System (ADS)
Michaelides, Katerina; Martin, Gareth J.
2012-09-01
Hillslopes supply sediment to river channels, and therefore impact drainage basin functioning and evolution. The relationship between hillslope attributes and sediment flux forms the basis of geomorphic transport laws used to model the long-term topographic evolution of drainage basins, but their specific interactions during individual storm events are not well understood. Runoff-driven erosion of coarse particles, prevalent in dryland environments, presents a particular set of conditions for sediment transport that is poorly resolved in current models. In order to address this gap, we developed a particle-based, force-balance model for sheetwash sediment transport on coarse, debris-mantled hillslopes within a rainfall-runoff model. We use the model to examine how the interplay between hillslope attributes (gradient, length and grain size distribution) and runoff characteristics affects sediment transport, grain-size changes on the hillslope, and sediment supply to the slope base. The relationship between sediment flux and hillslope gradient was found to transition from linear above a threshold to sigmoidal depending on hillslope length, initial grain sizes, and runoff characteristics. Grain sizes supplied to the slope base vary in a complex manner with hillslope attributes but an overall coarsening of the hillslopes is found to occur with increasing gradient, corroborating previous findings from field measurements. Intense, short duration storms result in within-hillslope sediment redistribution and equifinality in sediment supply for different hillslope characteristics, which explain the lack of field evidence for any systematic relationships. Our model findings provide insights into hillslope responses to climatic forcing and have theoretical implications for modeling hillslope evolution in dry lands.
Promising Ta-Ti-Zr-Si metallic glass coating without cytotoxic elements for bio-implant applications
NASA Astrophysics Data System (ADS)
Lai, J. J.; Lin, Y. S.; Chang, C. H.; Wei, T. Y.; Huang, J. C.; Liao, Z. X.; Lin, C. H.; Chen, C. H.
2018-01-01
Tantalum (Ta) is considered as one of the most promising metal due to its high corrosion resistance, excellent biocompatibility and cell adhesion/in-growth capabilities. Although there are some researches exploring the biomedical aspects of Ta and Ta based alloys, systematic characterizations of newly developed Ta-based metallic glasses in bio-implant applications is still lacking. This study employs sputtering approach to produced thin-film Ti-based metallic glasses due to the high melting temperature of Ta (3020 °C). Two fully amorphous Ta-based metallic glasses composed of Ta57Ti17Zr15Si11 and Ta75Ti10Zr8Si7 are produced and experimentally characterized in terms of their mechanical properties, bio-corrosion properties, surface hydrophilic characteristics, and in-vitro cell viability and cells attachment tests. Compare to conventional pure Ti and Ta metals, the developed Ta-based metallic glasses exhibit higher hardness and lower modulus which are better match to the mechanical properties of bone. MTS assay results show that Ta-based metallic glasses show comparable cell viability and cell attachment rate compared to that of pure Ti and Ta surface in a 72 h in-vitro test.
NASA Astrophysics Data System (ADS)
Liao, G. K.; Long, Z. L.; Zhao, M. S. Z.; Peng, L.; Chai, W.; Ping, Z. H.
2018-04-01
This paper presents the research on the evolution of shear transformation zone (STZ) in a Pd-based bulk metallic glass (BMG) during serrated flow under nanoindentation. A novel method of estimating the STZ volume through statistical analysis of the serrated flow behavior was proposed for the first time. Based on the proposed method, the STZ volume of the studied BMG at various peak loads have been systematically investigated. The results indicate that the measured STZ volumes are in good agreement with that documented in literature, and the STZ size exhibits an increasing trend during indentation. Moreover, the correlation between the serrated flow dynamics and the STZ activation has also been evaluated. It is found that the STZ activation can promote the formation of self-organized critical (SOC) state during serrated flow.
Neutrino and axion bounds from the globular cluster M5 (NGC 5904).
Viaux, N; Catelan, M; Stetson, P B; Raffelt, G G; Redondo, J; Valcarce, A A R; Weiss, A
2013-12-06
The red-giant branch (RGB) in globular clusters is extended to larger brightness if the degenerate helium core loses too much energy in "dark channels." Based on a large set of archival observations, we provide high-precision photometry for the Galactic globular cluster M5 (NGC 5904), allowing for a detailed comparison between the observed tip of the RGB with predictions based on contemporary stellar evolution theory. In particular, we derive 95% confidence limits of g(ae)<4.3×10(-13) on the axion-electron coupling and μ(ν)<4.5×10(-12)μ(B) (Bohr magneton μ(B)=e/2m(e)) on a neutrino dipole moment, based on a detailed analysis of statistical and systematic uncertainties. The cluster distance is the single largest source of uncertainty and can be improved in the future.
Cost-effective conservation of amphibian ecology and evolution
Campos, Felipe S.; Lourenço-de-Moraes, Ricardo; Llorente, Gustavo A.; Solé, Mirco
2017-01-01
Habitat loss is the most important threat to species survival, and the efficient selection of priority areas is fundamental for good systematic conservation planning. Using amphibians as a conservation target, we designed an innovative assessment strategy, showing that prioritization models focused on functional, phylogenetic, and taxonomic diversity can include cost-effectiveness–based assessments of land values. We report new key conservation sites within the Brazilian Atlantic Forest hot spot, revealing a congruence of ecological and evolutionary patterns. We suggest payment for ecosystem services through environmental set-asides on private land, establishing potential trade-offs for ecological and evolutionary processes. Our findings introduce additional effective area-based conservation parameters that set new priorities for biodiversity assessment in the Atlantic Forest, validating the usefulness of a novel approach to cost-effectiveness–based assessments of conservation value for other species-rich regions. PMID:28691084
Evolution of the amniote pallium and the origins of mammalian neocortex
Butler, Ann B.; Reiner, Anton; Karten, Harvey J.
2012-01-01
Karten's neocortex hypothesis holds that many component cell populations of the sauropsid dorsal ventricular ridge (DVR) are homologous to particular cell populations in layers of auditory and visual tectofugal-recipient neocortex of mammals (i.e., temporal neocortex), as well as to some amygdaloid populations. The claustroamygdalar hypothesis, based on gene expression domains, proposes that mammalian homologues of DVR are found in the claustrum, endopiriform nuclei, and/or pallial amygdala. Because hypotheses of homology need to account for the totality of the evidence, the available data on multiple forebrain features of sauropsids and mammals are reviewed here. While some genetic data are compatible with the claustroamygdalar hypothesis, and developmental (epigenetic) data are indecisive, hodological, morphological, and topographical data favor the neocortex hypothesis and are inconsistent with the claustroamygdalar hypothesis. Detailed studies of gene signaling cascades that establish neuronal cell-type identity in DVR, tectofugal-recipient neocortex, and claustroamygdala will be needed to resolve this debate about the evolution of neocortex. PMID:21534989
Dispersal-competition tradeoff in microbiomes in the quest for land colonization.
Dini-Andreote, Francisco; van Elsas, Jan Dirk; Olff, Han; Salles, Joana Falcão
2018-06-21
Ancestor microbes started colonizing inland habitats approximately 2.7 to 3.5 billion years ago. With some exceptions, the key physiological adaptations of microbiomes associated with marine-to-land transitions have remained elusive. This is essentially caused by the lack of suitable systems that depict changes in microbiomes across sufficiently large time scales. Here, we investigate the adaptive routes taken by microbiomes along a contemporary gradient of land formation. Using functional trait-based metagenomics, we show that a switch from a microbial 'dispersal' to a 'competition' response modus best characterizes the microbial trait changes during this eco-evolutionary trajectory. The 'dispersal' modus prevails in microbiomes at the boundary sites between land and sea. It encompasses traits conferring cell chemosensory and motile behaviors, thus allowing the local microbes to exploit short-lived nutritional patches in high-diffusion microhabitats. A systematic transition towards the 'competition' modus occurs progressively as the soil matures, which is likely due to forces of viscosity or strain that favor traits for competition and chemical defense. Concomitantly, progressive increases in the abundances of genes encoding antibiotic resistance and complex organic substrate degradation were found. Our findings constitute a novel perspective on the ecology and evolution of microbiome traits, tracking back one of the most seminal transitions in the evolutionary history of life.
Neocortical neuron types in Xenarthra and Afrotheria: implications for brain evolution in mammals.
Sherwood, Chet C; Stimpson, Cheryl D; Butti, Camilla; Bonar, Christopher J; Newton, Alisa L; Allman, John M; Hof, Patrick R
2009-02-01
Interpreting the evolution of neuronal types in the cerebral cortex of mammals requires information from a diversity of species. However, there is currently a paucity of data from the Xenarthra and Afrotheria, two major phylogenetic groups that diverged close to the base of the eutherian mammal adaptive radiation. In this study, we used immunohistochemistry to examine the distribution and morphology of neocortical neurons stained for nonphosphorylated neurofilament protein, calbindin, calretinin, parvalbumin, and neuropeptide Y in three xenarthran species-the giant anteater (Myrmecophaga tridactyla), the lesser anteater (Tamandua tetradactyla), and the two-toed sloth (Choloepus didactylus)-and two afrotherian species-the rock hyrax (Procavia capensis) and the black and rufous giant elephant shrew (Rhynchocyon petersi). We also studied the distribution and morphology of astrocytes using glial fibrillary acidic protein as a marker. In all of these species, nonphosphorylated neurofilament protein-immunoreactive neurons predominated in layer V. These neurons exhibited diverse morphologies with regional variation. Specifically, high proportions of atypical neurofilament-enriched neuron classes were observed, including extraverted neurons, inverted pyramidal neurons, fusiform neurons, and other multipolar types. In addition, many projection neurons in layers II-III were found to contain calbindin. Among interneurons, parvalbumin- and calbindin-expressing cells were generally denser compared to calretinin-immunoreactive cells. We traced the evolution of certain cortical architectural traits using phylogenetic analysis. Based on our reconstruction of character evolution, we found that the living xenarthrans and afrotherians show many similarities to the stem eutherian mammal, whereas other eutherian lineages display a greater number of derived traits.
Modeling crust-mantle evolution using radiogenic Sr, Nd, and Pb isotope systematics
NASA Astrophysics Data System (ADS)
Kumari, Seema; Paul, Debajyoti
2015-04-01
The present-day elemental and isotopic composition of Earth's terrestrial reservoirs can be used as geochemical constraints to study evolution of the crust-mantle system. A flexible open system evolutionary model of the Earth, comprising continental crust (CC), upper depleted mantle (UM) -source of mid-ocean ridge basalts (MORB), and lower mantle (LM) reservoir with a D" layer -source of ocean island basalts (OIB), and incorporating key radioactive isotope systematics (Rb-Sr, Sm-Nd, and U-Th-Pb), is solved numerically at 1 Ma time step for 4.55 Ga, the age of the Earth. The best possible solution is the one that produces the present-day concentrations as well as isotopic ratios in terrestrial reservoirs, compiled from published data. Different crustal growth scenarios (exponential, episodic, early and late growth), proposed in earlier studies, and its effect on the evolution of isotope systematics of terrestrial reservoirs is studied. Model simulations strongly favor a layered mantle structure satisfying majority of the isotopic constraints. In the successful model, which is similar to that proposed by Kellogg et al. (1999), the present-day UM comprises of 60% of mantle mass and extends to a depth 1600 km, whereas the LM becomes non-primitive and more enriched than the bulk silicate Earth, mainly due to addition of recycled crustal material. Modeling suggest that isotopic evolution of reservoirs is affected by the mode of crustal growth. Only two scenarios satisfied majority of the Rb-Sr and Sm-Nd isotopic constraints but failed to reproduce the present-day Pb-isotope systematics; exponential growth of crust (mean age, tc=2.3 Ga) and delayed and episodic growth (no growth for initial 900 Ma, tc=2.05 Ga) proposed by Patchett and Arndt (1986). However, assuming a slightly young Earth (4.45 Ga) better satisfies the Pb-isotope systematics. Although, the delayed crustal growth model satisfied Sr-Nd isotopic constraints, presence of early Hadean crust (4.03 and 4.4 Ga detrital zircon in Acasta gneiss and Yilgarn block, respectively), argues against it. One notable feature of successful models is an early depletion of incompatible elements (as well as Th/U ratio in the UM) by the initial 500 Ma, as a result of early formation of continental crust. Our results strongly favor exponential crustal growth and layered mantle structure. Patchett, P.J., Arndt, N.T. (1986), Earth and Planetary Science Letters, 78, 329-338. Kellogg, L.H., Hager, B.H., van der Hilst, R.D (1999), Science, 283, 1881-1884.
The visual system of the Australian 'Redeye' cicada (Psaltoda moerens).
Ribi, Willi A; Zeil, Jochen
2015-11-01
We investigated the functional anatomy of the visual system in the Australian 'Redeye' cicada Psaltoda moerens, including compound eyes and ocelli. The compound eyes have large visual fields, about 7500 ommatidia per eye and binocular overlaps of 10-15° in the frontal and of 50-60° in the dorsal visual field. The diameters of corneal facet lenses range between 22 and 34 μm and the lenses are unusually long with up to 100 μm in some eye regions. In the posterior part of the eyes, the hexagonal facet array changes to a square lattice. The compound eyes are of the eucone apposition type with 8 retinular cells contributing to a fused rhabdom in each ommatidium. The red eye colour is due to the pigment granules in the secondary pigment cells. We found a small Dorsal Rim Area (DRA), in which rhabdom cross-sections are rectangular rather than round. The cross-sections of DRA rhabdoms do not systematically change orientation along the length of the rhabdom, indicating that microvilli directions do not twist, which would make retinular cells in the DRA polarization sensitive. The three ocelli have unusual lenses with a champagne-cork shape in longitudinal sections. Retinular cells are short in the dorsal and ventral part of the retinae, and long in their equatorial part. Ocellar rhabdoms are short (<10 μm), positioned close to the corneagenous layer and are formed by pairs of retinular cells. In cross-section, the rhabdomeres are 2-5 μm long and straight. The red colour of ocelli is produced by screening pigments that form an iris around the base of the ocellar lens and by screening pigments between the ocellar retinular cells. We discuss the organization of the compound eye rhabdom, the organization of the ocelli and the presence of a DRA in the light of what is known about Hemipteran compound eyes. We note in particular that cicadas are the only Hemipteran group with fused rhabdoms, thus making Hemiptera an interesting case to study the evolution of open rhabdoms and neural superposition. Copyright © 2015 Elsevier Ltd. All rights reserved.
Mizas, Ch; Sirakoulis, G Ch; Mardiris, V; Karafyllidis, I; Glykos, N; Sandaltzopoulos, R
2008-04-01
Change of DNA sequence that fuels evolution is, to a certain extent, a deterministic process because mutagenesis does not occur in an absolutely random manner. So far, it has not been possible to decipher the rules that govern DNA sequence evolution due to the extreme complexity of the entire process. In our attempt to approach this issue we focus solely on the mechanisms of mutagenesis and deliberately disregard the role of natural selection. Hence, in this analysis, evolution refers to the accumulation of genetic alterations that originate from mutations and are transmitted through generations without being subjected to natural selection. We have developed a software tool that allows modelling of a DNA sequence as a one-dimensional cellular automaton (CA) with four states per cell which correspond to the four DNA bases, i.e. A, C, T and G. The four states are represented by numbers of the quaternary number system. Moreover, we have developed genetic algorithms (GAs) in order to determine the rules of CA evolution that simulate the DNA evolution process. Linear evolution rules were considered and square matrices were used to represent them. If DNA sequences of different evolution steps are available, our approach allows the determination of the underlying evolution rule(s). Conversely, once the evolution rules are deciphered, our tool may reconstruct the DNA sequence in any previous evolution step for which the exact sequence information was unknown. The developed tool may be used to test various parameters that could influence evolution. We describe a paradigm relying on the assumption that mutagenesis is governed by a near-neighbour-dependent mechanism. Based on the satisfactory performance of our system in the deliberately simplified example, we propose that our approach could offer a starting point for future attempts to understand the mechanisms that govern evolution. The developed software is open-source and has a user-friendly graphical input interface.
Metabolic design of macroscopic bioreaction models: application to Chinese hamster ovary cells.
Provost, A; Bastin, G; Agathos, S N; Schneider, Y-J
2006-12-01
The aim of this paper is to present a systematic methodology to design macroscopic bioreaction models for cell cultures based upon metabolic networks. The cell culture is seen as a succession of phases. During each phase, a metabolic network represents the set of reactions occurring in the cell. Then, through the use of the elementary flux modes, these metabolic networks are used to derive macroscopic bioreactions linking the extracellular substrates and products. On this basis, as many separate models are obtained as there are phases. Then, a complete model is obtained by smoothly switching from model to model. This is illustrated with batch cultures of Chinese hamster ovary cells.
A Stochastic Framework for Modeling the Population Dynamics of Convective Clouds
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hagos, Samson; Feng, Zhe; Plant, Robert S.
A stochastic prognostic framework for modeling the population dynamics of convective clouds and representing them in climate models is proposed. The approach used follows the non-equilibrium statistical mechanical approach through a master equation. The aim is to represent the evolution of the number of convective cells of a specific size and their associated cloud-base mass flux, given a large-scale forcing. In this framework, referred to as STOchastic framework for Modeling Population dynamics of convective clouds (STOMP), the evolution of convective cell size is predicted from three key characteristics: (i) the probability of growth, (ii) the probability of decay, and (iii)more » the cloud-base mass flux. STOMP models are constructed and evaluated against CPOL radar observations at Darwin and convection permitting model (CPM) simulations. Multiple models are constructed under various assumptions regarding these three key parameters and the realisms of these models are evaluated. It is shown that in a model where convective plumes prefer to aggregate spatially and mass flux is a non-linear function of convective cell area, mass flux manifests a recharge-discharge behavior under steady forcing. Such a model also produces observed behavior of convective cell populations and CPM simulated mass flux variability under diurnally varying forcing. Besides its use in developing understanding of convection processes and the controls on convective cell size distributions, this modeling framework is also designed to be capable of providing alternative, non-equilibrium, closure formulations for spectral mass flux parameterizations.« less