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
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
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
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.
Luo, Zhaofeng; Zhou, Hongmin; Jiang, Hao; Ou, Huichao; Li, Xin; Zhang, Liyun
2015-04-21
Aptamers have attracted much attention due to their ability to bind to target molecules with high affinity and specificity. The development of an approach capable of efficiently generating aptamers through systematic evolution of ligands by exponential enrichment (SELEX) is particularly challenging. Herein, a fraction collection approach in capillary electrophoresis SELEX (FCE-SELEX) for the partition of a bound DNA-target complex is developed. By integrating fraction collection with a facile oil seal method for avoiding contamination while amplifying the bound DNA-target complex, in a single round of selection, a streptavidin-binding aptamer (SBA) has been generated. The affinity of aptamer SBA-36 for streptavidin (SA) is determined as 30.8 nM by surface plasmon resonance (SPR). Selectivity and biotin competition experiments demonstrate that the SBA-36 aptamer selected by FCE-SELEX is as efficient as those from other methods. Based on the ability of fraction collection in partition and collection of the aptamer-target complex from the original DNA library, FCE-SELEX can be a universal tool for the development of aptamers.
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.
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
Large scale analysis of the mutational landscape in HT-SELEX improves aptamer discovery
Hoinka, Jan; Berezhnoy, Alexey; Dao, Phuong; Sauna, Zuben E.; Gilboa, Eli; Przytycka, Teresa M.
2015-01-01
High-Throughput (HT) SELEX combines SELEX (Systematic Evolution of Ligands by EXponential Enrichment), a method for aptamer discovery, with massively parallel sequencing technologies. This emerging technology provides data for a global analysis of the selection process and for simultaneous discovery of a large number of candidates but currently lacks dedicated computational approaches for their analysis. To close this gap, we developed novel in-silico methods to analyze HT-SELEX data and utilized them to study the emergence of polymerase errors during HT-SELEX. Rather than considering these errors as a nuisance, we demonstrated their utility for guiding aptamer discovery. Our approach builds on two main advancements in aptamer analysis: AptaMut—a novel technique allowing for the identification of polymerase errors conferring an improved binding affinity relative to the ‘parent’ sequence and AptaCluster—an aptamer clustering algorithm which is to our best knowledge, the only currently available tool capable of efficiently clustering entire aptamer pools. We applied these methods to an HT-SELEX experiment developing aptamers against Interleukin 10 receptor alpha chain (IL-10RA) and experimentally confirmed our predictions thus validating our computational methods. PMID:25870409
Capture-SELEX: Selection of DNA Aptamers for Aminoglycoside Antibiotics
2012-01-01
Small organic molecules are challenging targets for an aptamer selection using the SELEX technology (SELEX—Systematic Evolution of Ligans by EXponential enrichment). Often they are not suitable for immobilization on solid surfaces, which is a common procedure in known aptamer selection methods. The Capture-SELEX procedure allows the selection of DNA aptamers for solute targets. A special SELEX library was constructed with the aim to immobilize this library on magnetic beads or other surfaces. For this purpose a docking sequence was incorporated into the random region of the library enabling hybridization to a complementary oligo fixed on magnetic beads. Oligonucleotides of the library which exhibit high affinity to the target and a secondary structure fitting to the target are released from the beads for binding to the target during the aptamer selection process. The oligonucleotides of these binding complexes were amplified, purified, and immobilized via the docking sequence to the magnetic beads as the starting point of the following selection round. Based on this Capture-SELEX procedure, the successful DNA aptamer selection for the aminoglycoside antibiotic kanamycin A as a small molecule target is described. PMID:23326761
Simple Methods and Rational Design for Enhancing Aptamer Sensitivity and Specificity
Kalra, Priya; Dhiman, Abhijeet; Cho, William C.; Bruno, John G.; Sharma, Tarun K.
2018-01-01
Aptamers are structured nucleic acid molecules that can bind to their targets with high affinity and specificity. However, conventional SELEX (Systematic Evolution of Ligands by EXponential enrichment) methods may not necessarily produce aptamers of desired affinity and specificity. Thus, to address these questions, this perspective is intended to suggest some approaches and tips along with novel selection methods to enhance evolution of aptamers. This perspective covers latest novel innovations as well as a broad range of well-established approaches to improve the individual binding parameters (aptamer affinity, avidity, specificity and/or selectivity) of aptamers during and/or post-SELEX. The advantages and limitations of individual aptamer selection methods and post-SELEX optimizations, along with rational approaches to overcome these limitations are elucidated in each case. Further the impact of chosen selection milieus, linker-systems, aptamer cocktails and detection modules utilized in conjunction with target-specific aptamers, on the overall assay performance are discussed in detail, each with its own advantages and limitations. The simple variations suggested are easily available for facile implementation during and/or post-SELEX to develop ultrasensitive and specific assays. Finally, success studies of established aptamer-based assays are discussed, highlighting how they utilized some of the suggested methodologies to develop commercially successful point-of-care diagnostic assays. PMID:29868605
Simple Methods and Rational Design for Enhancing Aptamer Sensitivity and Specificity.
Kalra, Priya; Dhiman, Abhijeet; Cho, William C; Bruno, John G; Sharma, Tarun K
2018-01-01
Aptamers are structured nucleic acid molecules that can bind to their targets with high affinity and specificity. However, conventional SELEX (Systematic Evolution of Ligands by EXponential enrichment) methods may not necessarily produce aptamers of desired affinity and specificity. Thus, to address these questions, this perspective is intended to suggest some approaches and tips along with novel selection methods to enhance evolution of aptamers. This perspective covers latest novel innovations as well as a broad range of well-established approaches to improve the individual binding parameters (aptamer affinity, avidity, specificity and/or selectivity) of aptamers during and/or post-SELEX. The advantages and limitations of individual aptamer selection methods and post-SELEX optimizations, along with rational approaches to overcome these limitations are elucidated in each case. Further the impact of chosen selection milieus, linker-systems, aptamer cocktails and detection modules utilized in conjunction with target-specific aptamers, on the overall assay performance are discussed in detail, each with its own advantages and limitations. The simple variations suggested are easily available for facile implementation during and/or post-SELEX to develop ultrasensitive and specific assays. Finally, success studies of established aptamer-based assays are discussed, highlighting how they utilized some of the suggested methodologies to develop commercially successful point-of-care diagnostic assays.
Identification of sequence-structure RNA binding motifs for SELEX-derived aptamers.
Hoinka, Jan; Zotenko, Elena; Friedman, Adam; Sauna, Zuben E; Przytycka, Teresa M
2012-06-15
Systematic Evolution of Ligands by EXponential Enrichment (SELEX) represents a state-of-the-art technology to isolate single-stranded (ribo)nucleic acid fragments, named aptamers, which bind to a molecule (or molecules) of interest via specific structural regions induced by their sequence-dependent fold. This powerful method has applications in designing protein inhibitors, molecular detection systems, therapeutic drugs and antibody replacement among others. However, full understanding and consequently optimal utilization of the process has lagged behind its wide application due to the lack of dedicated computational approaches. At the same time, the combination of SELEX with novel sequencing technologies is beginning to provide the data that will allow the examination of a variety of properties of the selection process. To close this gap we developed, Aptamotif, a computational method for the identification of sequence-structure motifs in SELEX-derived aptamers. To increase the chances of identifying functional motifs, Aptamotif uses an ensemble-based approach. We validated the method using two published aptamer datasets containing experimentally determined motifs of increasing complexity. We were able to recreate the author's findings to a high degree, thus proving the capability of our approach to identify binding motifs in SELEX data. Additionally, using our new experimental dataset, we illustrate the application of Aptamotif to elucidate several properties of the selection process.
Post-SELEX optimization of aptamers.
Gao, Shunxiang; Zheng, Xin; Jiao, Binghua; Wang, Lianghua
2016-07-01
Aptamers are functional single-stranded DNA or RNA oligonucleotides, selected in vitro by SELEX (Systematic Evolution of Ligands by Exponential Enrichment), which can fold into stable unique three-dimensional structures that bind their target ligands with high affinity and specificity. Although aptamers show a number of favorable advantages such as better stability and easier modification when compared with the properties of antibodies, only a handful of aptamers have entered clinical trials and only one, pegaptanib, has received US Food and Drug Administration approval for clinical use. The main reasons that limit the practical application of aptamers are insufficient nuclease stability, bioavailability, thermal stability, or even affinity. Some aptamers obtained from modified libraries show better properties; however, polymerase amplification of nucleic acids containing non-natural bases is currently a primary drawback of the SELEX process. This review focuses on several post-SELEX optimization strategies of aptamers identified in recent years. We describe four common methods in detail: truncation, chemical modification, bivalent or multivalent aptamer construction, and mutagenesis. We believe that these optimization strategies should improve one or more specific properties of aptamers, and the type of feature(s) selected for improvement will be dependent on the application purpose.
Identification of sequence–structure RNA binding motifs for SELEX-derived aptamers
Hoinka, Jan; Zotenko, Elena; Friedman, Adam; Sauna, Zuben E.; Przytycka, Teresa M.
2012-01-01
Motivation: Systematic Evolution of Ligands by EXponential Enrichment (SELEX) represents a state-of-the-art technology to isolate single-stranded (ribo)nucleic acid fragments, named aptamers, which bind to a molecule (or molecules) of interest via specific structural regions induced by their sequence-dependent fold. This powerful method has applications in designing protein inhibitors, molecular detection systems, therapeutic drugs and antibody replacement among others. However, full understanding and consequently optimal utilization of the process has lagged behind its wide application due to the lack of dedicated computational approaches. At the same time, the combination of SELEX with novel sequencing technologies is beginning to provide the data that will allow the examination of a variety of properties of the selection process. Results: To close this gap we developed, Aptamotif, a computational method for the identification of sequence–structure motifs in SELEX-derived aptamers. To increase the chances of identifying functional motifs, Aptamotif uses an ensemble-based approach. We validated the method using two published aptamer datasets containing experimentally determined motifs of increasing complexity. We were able to recreate the author's findings to a high degree, thus proving the capability of our approach to identify binding motifs in SELEX data. Additionally, using our new experimental dataset, we illustrate the application of Aptamotif to elucidate several properties of the selection process. Contact: przytyck@ncbi.nlm.nih.gov, Zuben.Sauna@fda.hhs.gov PMID:22689764
Zhang, Lu; Xu, Jinhao; Ma, Jinbiao
2016-07-25
RNA-binding protein exerts important biological function by specifically recognizing RNA motif. SELEX (Systematic evolution of ligands by exponential enrichment), an in vitro selection method, can obtain consensus motif with high-affinity and specificity for many target molecules from DNA or RNA libraries. Here, we combined SELEX with next-generation sequencing to study the protein-RNA interaction in vitro. A pool of RNAs with 20 bp random sequences were transcribed by T7 promoter, and target protein was inserted into plasmid containing SBP-tag, which can be captured by streptavidin beads. Through only one cycle, the specific RNA motif can be obtained, which dramatically improved the selection efficiency. Using this method, we found that human hnRNP A1 RRMs domain (UP1 domain) bound RNA motifs containing AGG and AG sequences. The EMSA experiment indicated that hnRNP A1 RRMs could bind the obtained RNA motif. Taken together, this method provides a rapid and effective method to study the RNA binding specificity of proteins.
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.
Breast Cancer Translational Research Center of Excellence
2015-09-01
we will identify partner proteins by either Y2H or pull-down studies using Mass Spectrometry Analysis. Aim 2. Development of DNA aptamers against...CD44 that inhibit breast cancer invasion and metastasis. During the previous period, we developed novel and unique DNA aptamers that specifically...bound to exon v10 of CD44 using Systematic Evolution of Ligands by Exponential Enrichment (SELEX) systems. These DNA aptamers inhibited TN breast
Recent trends in SELEX technique and its application to food safety monitoring
Mei, Zhanlong; Yao, Li; Wang, Xin; Zheng, Lei; Liu, Jian; Liu, Guodong; Peng, Chifang; Chen, Wei
2014-01-01
The method referred to as “systemic evolution of ligands by exponential enrichment” (SELEX) was introduced in 1990 and ever since has become an important tool for the identification and screening of aptamers. Such nucleic acids can recognize and bind to their corresponding targets (analytes) with high selectivity and affinity, and aptamers therefore have become attractive alternatives to traditional antibodies not the least because they are much more stable. Meanwhile, they have found numerous applications in different fields including food quality and safety monitoring. This review first gives an introduction into the selection process and to the evolution of SELEX, then covers applications of aptamers in the surveillance of food safety (with subsections on absorptiometric, electrochemical, fluorescent and other methods), and then gives conclusions and perspectives. The SELEX method excels by its features of in vitro, high throughput and ease of operation. This review contains 86 references. PMID:25419005
Advances in aptamer screening and small molecule aptasensors.
Kim, Yeon Seok; Gu, Man Bock
2014-01-01
It has been 20 years since aptamer and SELEX (systematic evolution of ligands by exponential enrichment) were described independently by Andrew Ellington and Larry Gold. Based on the great advantages of aptamers, there have been numerous isolated aptamers for various targets that have actively been applied as therapeutic and analytical tools. Over 2,000 papers related to aptamers or SELEX have been published, attesting to their wide usefulness and the applicability of aptamers. SELEX methods have been modified or re-created over the years to enable aptamer isolation with higher affinity and selectivity in more labor- and time-efficient manners, including automation. Initially, most of the studies about aptamers have focused on the protein targets, which have physiological functions in the body, and their applications as therapeutic agents or receptors for diagnostics. However, aptamers for small molecules such as organic or inorganic compounds, drugs, antibiotics, or metabolites have not been studied sufficiently, despite the ever-increasing need for rapid and simple analytical methods for various chemical targets in the fields of medical diagnostics, environmental monitoring, food safety, and national defense against targets including chemical warfare. This review focuses on not only recent advances in aptamer screening methods but also its analytical application for small molecules.
Selection and characterization of a DNA aptamer to crystal violet.
Chen, Yang; Wang, Jine; Zhang, Yajie; Xu, Lijun; Gao, Tian; Wang, Bing; Pei, Renjun
2018-06-13
Aptamers are short single-stranded DNA or RNA, which can be selected in vitro by systematic evolution of ligands by exponential enrichment (SELEX). In order to develop novel light-up probes to substitute G-quadruplex (G4), we selected a DNA aptamer for crystal violet (CV), a triphenylmethane light-up dye, by a modified affinity chromatography-based SELEX. The ssDNA pool was first coupled on streptavidin-coated agarose beads through a biotin labeled complementary oligonucleotide, and then the aptamer sequences would be released from agarose beads by CV affinity. This method is simple, straightforward and effective. The aptamer sequence with a low micromolar dissociation constant (Kd) and good specificity was achieved after 11 rounds of selection. The light-up properties of the CV-aptamer were also investigated, and the CV showed dramatic fluorescence enhancement. The CV-aptamer pair could be further used as a novel light-up fluorescent probe to design biosensors.
[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.
Aptamer-based technology for food analysis.
Liu, Xiaofei; Zhang, Xuewu
2015-01-01
Aptamers are short and functional single-stranded oligonucleotide sequences selected from systematic evolution of ligands by exponential enrichment (SELEX) process, which have the capacity to recognize various classes of target molecules with high affinity and specificity. Various analytical aptamers acquired by SELEX are widely used in many research fields, such as medicine, biology, and chemistry. However, the application of this innovative and emerging technology to food safety is just in infant stage. Food safety plays a very important role in our daily lives because varieties of poisonous and harmful substances in food affect human health. Aptamer technique is promising, which can overcome many disadvantages of existing detection methods in food safety, such as long detection time, low sensitivity, difficult, and expensive antibody preparation. This review provides an overview of various aptamer screening technologies and summarizes the recent applications of aptamers in food safety, and future prospects are also discussed.
NASA Astrophysics Data System (ADS)
Gu, Huajie; Duan, Nuo; Wu, Shijia; Hao, Liling; Xia, Yu; Ma, Xiaoyuan; Wang, Zhouping
2016-02-01
Okadaic acid (OA) is a low-molecular-weight marine toxin from shellfish that causes abdominal pain, vomiting and diarrhea, i.e., diarrheic shellfish poisoning. In this study, a ssDNA aptamer that specifically binds to OA with high affinity was obtained via Systematic Evolution of Ligands by Exponential Enrichment (SELEX) assisted by graphene oxide (GO). This aptamer was then applied to fabricate a novel direct competitive enzyme-linked aptamer assay (ELAA). At the optimized conditions, this ELAA method showed a low detection limit (LOD of 0.01 ng/mL), wide linear range (from 0.025 to 10 ng/mL), good recovery rate (92.86-103.34% in OA-spiked clam samples) and repeatability (RSD of 2.28-4.53%). The proposed method can be used to detect OA in seafood products with high sensitivity and can potentially be adapted for the determination of other small molecular analytes.
Chang, Tzuu-Wang; Janardhanan, Pavithra; Mello, Charlene M; Singh, Bal Ram; Cai, Shuowei
2016-09-01
Botulinum neurotoxin (BoNT), a category A agent, is the most toxic molecule known to mankind. The endopeptidase activity of light chain domain of BoNT is the cause for the inhibition of the neurotransmitter release and the flaccid paralysis that leads to lethality in botulism. Currently, antidotes are not available to reverse the flaccid paralysis caused by BoNT. In the present study, a non-radioactive-based systematic evolution of ligands by exponential enrichment (SELEX) process is developed by utilizing surface plasmon resonance to monitor the binding enrichment. Two RNA aptamers have been identified as strong binders against light chain of botulinum neurotoxin type A. These two aptamers showed strong inhibition activity on LCA, with IC50 in nanomolar range. Inhibition kinetic studies reveal mid nanomolar KI and non-competitive nature of their inhibition, suggesting that they have strong potential as antidotes that can reverse the symptom caused by BoNT/A. More importantly, we observed that the 2'-fluorine-pyrimidine-modified RNA aptamers identified here do not change their binding and biological activities. This observation could lead to a cost-effective way for SELEX, by using regular nucleotide during SELEX, and 2'-fluorine-pyrimidine-modified nucleotide for final application to enhance their RNase-resistance.
Chang, Tzuu-Wang; Janardhanan, Pavithra; Mello, Charlene; Singh, Bal Ram; Cai, Shuowei
2016-01-01
Botulinum neurotoxin (BoNT), a category A agent, is the most toxic molecule known to mankind. The endopeptidase activity of light chain domain of BoNT is the cause for the inhibition of the neurotransmitter release and the flaccid paralysis that leads to lethality in botulism. Currently, antidotes are not available to reverse the flaccid paralysis caused by BoNT. In the present study, a non-radioactive based SELEX process is developed by utilizing surface plasmon resonance to monitor the binding enrichment. Two RNA aptamers have been identified as strong binders against light chain of botulinum neurotoxin type A. These two aptamers showed strong inhibition activity on LCA, with IC50 in nM range. Inhibition kinetic studies reveal mid nanomolar KI and non-competitive nature of their inhibition, suggesting they have strong potential as antidotes that can reverse the symptom caused by BoNT/A. More importantly, we observed that 2′-fluorine-pyrimidines modified RNA aptamers identified here do not change their binding and biological activities. This observation could lead to a cost-effective way for Systematic Evolution of Ligands by EXponential enrichment (SELEX), by using regular nucleotide during SELEX, and 2′-fluorine-pyrimidines modified nucleotide for final application to enhance their RNase-resistance. PMID:27085355
Performing SELEX experiments in silico
NASA Astrophysics Data System (ADS)
Wondergem, J. A. J.; Schiessel, H.; Tompitak, M.
2017-11-01
Due to the sequence-dependent nature of the elasticity of DNA, many protein-DNA complexes and other systems in which DNA molecules must be deformed have preferences for the type of DNA sequence they interact with. SELEX (Systematic Evolution of Ligands by EXponential enrichment) experiments and similar sequence selection experiments have been used extensively to examine the (indirect readout) sequence preferences of, e.g., nucleosomes (protein spools around which DNA is wound for compactification) and DNA rings. We show how recently developed computational and theoretical tools can be used to emulate such experiments in silico. Opening up this possibility comes with several benefits. First, it allows us a better understanding of our models and systems, specifically about the roles played by the simulation temperature and the selection pressure on the sequences. Second, it allows us to compare the predictions made by the model of choice with experimental results. We find agreement on important features between predictions of the rigid base-pair model and experimental results for DNA rings and interesting differences that point out open questions in the field. Finally, our simulations allow application of the SELEX methodology to systems that are experimentally difficult to realize because they come with high energetic costs and are therefore unlikely to form spontaneously, such as very short or overwound DNA rings.
Agresti, Jeremy J.; Kelly, Bernard T.; Jäschke, Andres; Griffiths, Andrew D.
2005-01-01
In vitro compartmentalization (IVC) has previously been used to evolve protein enzymes. Here, we demonstrate how IVC can be applied to select RNA enzymes (ribozymes) for a property that has previously been unselectable: true intermolecular catalysis. Libraries containing 1011 ribozyme genes are compartmentalized in the aqueous droplets of a water-in-oil emulsion, such that most droplets contain no more than one gene, and transcribed in situ. By coencapsulating the gene, RNA, and the substrates/products of the catalyzed reaction, ribozymes can be selected for all enzymatic properties: substrate recognition, product formation, rate acceleration, and turnover. Here we exploit the complementarity of IVC with systematic evolution of ligands by exponential enrichment (SELEX), which allows selection of larger libraries (≥1015) and for very small rate accelerations (kcat/kuncat) but only selects for intramolecular single-turnover reactions. We selected ≈1014 random RNAs for Diels–Alderase activity with five rounds of SELEX, then six to nine rounds with IVC. All selected ribozymes catalyzed the Diels–Alder reaction in a truly bimolecular fashion and with multiple turnover. Nearly all ribozymes selected by using eleven rounds of SELEX alone contain a common catalytic motif. Selecting with SELEX then IVC gave ribozymes with significant sequence variations in this catalytic motif and ribozymes with completely novel motifs. Interestingly, the catalytic properties of all of the selected ribozymes were quite similar. The ribozymes are strongly product inhibited, consistent with the Diels–Alder transition state closely resembling the product. More efficient Diels–Alderases may need to catalyze a second reaction that transforms the product and prevents product inhibition. PMID:16260754
2018-01-01
New, as yet undiscovered aptamers for Protein A were identified by applying next generation sequencing (NGS) to a previously selected aptamer pool. This pool was obtained in a classical SELEX (Systematic Evolution of Ligands by EXponential enrichment) experiment using the FluMag-SELEX procedure followed by cloning and Sanger sequencing. PA#2/8 was identified as the only Protein A-binding aptamer from the Sanger sequence pool, and was shown to be able to bind intact cells of Staphylococcus aureus. In this study, we show the extension of the SELEX results by re-sequencing of the same aptamer pool using a medium throughput NGS approach and data analysis. Both data pools were compared. They confirm the selection of a highly complex and heterogeneous oligonucleotide pool and show consistently a high content of orphans as well as a similar relative frequency of certain sequence groups. But in contrast to the Sanger data pool, the NGS pool was clearly dominated by one sequence group containing the known Protein A-binding aptamer PA#2/8 as the most frequent sequence in this group. In addition, we found two new sequence groups in the NGS pool represented by PA-C10 and PA-C8, respectively, which also have high specificity for Protein A. Comparative affinity studies reveal differences between the aptamers and confirm that PA#2/8 remains the most potent sequence within the selected aptamer pool reaching affinities in the low nanomolar range of KD = 20 ± 1 nM. PMID:29495282
Stoltenburg, Regina; Strehlitz, Beate
2018-02-24
New, as yet undiscovered aptamers for Protein A were identified by applying next generation sequencing (NGS) to a previously selected aptamer pool. This pool was obtained in a classical SELEX (Systematic Evolution of Ligands by EXponential enrichment) experiment using the FluMag-SELEX procedure followed by cloning and Sanger sequencing. PA#2/8 was identified as the only Protein A-binding aptamer from the Sanger sequence pool, and was shown to be able to bind intact cells of Staphylococcus aureus . In this study, we show the extension of the SELEX results by re-sequencing of the same aptamer pool using a medium throughput NGS approach and data analysis. Both data pools were compared. They confirm the selection of a highly complex and heterogeneous oligonucleotide pool and show consistently a high content of orphans as well as a similar relative frequency of certain sequence groups. But in contrast to the Sanger data pool, the NGS pool was clearly dominated by one sequence group containing the known Protein A-binding aptamer PA#2/8 as the most frequent sequence in this group. In addition, we found two new sequence groups in the NGS pool represented by PA-C10 and PA-C8, respectively, which also have high specificity for Protein A. Comparative affinity studies reveal differences between the aptamers and confirm that PA#2/8 remains the most potent sequence within the selected aptamer pool reaching affinities in the low nanomolar range of K D = 20 ± 1 nM.
DNA aptamers for the detection of Haemophilus influenzae type b by cell SELEX.
Bitaraf, F S; Rasooli, I; Mousavi Gargari, S L
2016-03-01
Haemophilus influenzae type b (Hib) causes acute bacterial meningitis (ABM) in children, with a mortality rate of about 3-6 % of the affected patients. ABM can lead to death during a period of hours to several days and, hence, rapid and early detection of the infection is crucial. Aptamers, the short single-stranded DNA or RNA with high affinity to target molecules, are selected by a high-flux screening technique known as in vitro screening and systematic evolution of ligands by exponential enrichment technology (SELEX). In this study, whole-cell SELEX was applied for the selection of target-specific aptamers with high affinity to Hib. ssDNA aptamers prepared by lambda exonuclease were incubated with the target cells (Hib). The aptameric binding rate to Hib was characterized for binding affinity after seven SELEX rounds by flow cytometry. The aptamers with higher binding affinity were cloned. Four of 68 aptamer clones were selected for sequencing. The dissociation constant (Kd) of the high-affinity aptamer clones 45 and 63 were 47.10 and 28.46 pM, respectively. These aptamers did not bind to other bacterial species, including the seven meningitis-causing bacteria. They showed distinct affinity to various H. influenzae strains only. These aptamers showed the highest affinity to Hib and the lowest affinity to H. influenzae type c and to other meningitis-causing bacteria. Clone 63 could detect Hib in patients' cerebrospinal fluid (CSF) samples at 60 colony-forming units (CFU)/mL. The results indicate applicability of the aptamers for rapid and early detection of infections brought about by Hib.
Moon, Jihea; Kim, Giyoung; Park, Saet Byeol; Lim, Jongguk; Mo, Changyeun
2015-01-01
Whole-cell Systemic Evolution of Ligands by Exponential enrichment (SELEX) is the process by which aptamers specific to target cells are developed. Aptamers selected by whole-cell SELEX have high affinity and specificity for bacterial surface molecules and live bacterial targets. To identify DNA aptamers specific to Staphylococcus aureus, we applied our rapid whole-cell SELEX method to a single-stranded ssDNA library. To improve the specificity and selectivity of the aptamers, we designed, selected, and developed two categories of aptamers that were selected by two kinds of whole-cell SELEX, by mixing and combining FACS analysis and a counter-SELEX process. Using this approach, we have developed a biosensor system that employs a high affinity aptamer for detection of target bacteria. FAM-labeled aptamer sequences with high binding to S. aureus, as determined by fluorescence spectroscopic analysis, were identified, and aptamer A14, selected by the basic whole-cell SELEX using a once-off FACS analysis, and which had a high binding affinity and specificity, was chosen. The binding assay was evaluated using FACS analysis. Our study demonstrated the development of a set of whole-cell SELEX derived aptamers specific to S. aureus; this approach can be used in the identification of other bacteria. PMID:25884791
Moon, Jihea; Kim, Giyoung; Park, Saet Byeol; Lim, Jongguk; Mo, Changyeun
2015-04-15
Whole-cell Systemic Evolution of Ligands by Exponential enrichment (SELEX) is the process by which aptamers specific to target cells are developed. Aptamers selected by whole-cell SELEX have high affinity and specificity for bacterial surface molecules and live bacterial targets. To identify DNA aptamers specific to Staphylococcus aureus, we applied our rapid whole-cell SELEX method to a single-stranded ssDNA library. To improve the specificity and selectivity of the aptamers, we designed, selected, and developed two categories of aptamers that were selected by two kinds of whole-cell SELEX, by mixing and combining FACS analysis and a counter-SELEX process. Using this approach, we have developed a biosensor system that employs a high affinity aptamer for detection of target bacteria. FAM-labeled aptamer sequences with high binding to S. aureus, as determined by fluorescence spectroscopic analysis, were identified, and aptamer A14, selected by the basic whole-cell SELEX using a once-off FACS analysis, and which had a high binding affinity and specificity, was chosen. The binding assay was evaluated using FACS analysis. Our study demonstrated the development of a set of whole-cell SELEX derived aptamers specific to S. aureus; this approach can be used in the identification of other bacteria.
Takahashi, Mayumi; Wu, Xiwei; Ho, Michelle; Chomchan, Pritsana; Rossi, John J; Burnett, John C; Zhou, Jiehua
2016-09-22
The systemic evolution of ligands by exponential enrichment (SELEX) technique is a powerful and effective aptamer-selection procedure. However, modifications to the process can dramatically improve selection efficiency and aptamer performance. For example, droplet digital PCR (ddPCR) has been recently incorporated into SELEX selection protocols to putatively reduce the propagation of byproducts and avoid selection bias that result from differences in PCR efficiency of sequences within the random library. However, a detailed, parallel comparison of the efficacy of conventional solution PCR versus the ddPCR modification in the RNA aptamer-selection process is needed to understand effects on overall SELEX performance. In the present study, we took advantage of powerful high throughput sequencing technology and bioinformatics analysis coupled with SELEX (HT-SELEX) to thoroughly investigate the effects of initial library and PCR methods in the RNA aptamer identification. Our analysis revealed that distinct "biased sequences" and nucleotide composition existed in the initial, unselected libraries purchased from two different manufacturers and that the fate of the "biased sequences" was target-dependent during selection. Our comparison of solution PCR- and ddPCR-driven HT-SELEX demonstrated that PCR method affected not only the nucleotide composition of the enriched sequences, but also the overall SELEX efficiency and aptamer efficacy.
Takahashi, Mayumi; Wu, Xiwei; Ho, Michelle; Chomchan, Pritsana; Rossi, John J.; Burnett, John C.; Zhou, Jiehua
2016-01-01
The systemic evolution of ligands by exponential enrichment (SELEX) technique is a powerful and effective aptamer-selection procedure. However, modifications to the process can dramatically improve selection efficiency and aptamer performance. For example, droplet digital PCR (ddPCR) has been recently incorporated into SELEX selection protocols to putatively reduce the propagation of byproducts and avoid selection bias that result from differences in PCR efficiency of sequences within the random library. However, a detailed, parallel comparison of the efficacy of conventional solution PCR versus the ddPCR modification in the RNA aptamer-selection process is needed to understand effects on overall SELEX performance. In the present study, we took advantage of powerful high throughput sequencing technology and bioinformatics analysis coupled with SELEX (HT-SELEX) to thoroughly investigate the effects of initial library and PCR methods in the RNA aptamer identification. Our analysis revealed that distinct “biased sequences” and nucleotide composition existed in the initial, unselected libraries purchased from two different manufacturers and that the fate of the “biased sequences” was target-dependent during selection. Our comparison of solution PCR- and ddPCR-driven HT-SELEX demonstrated that PCR method affected not only the nucleotide composition of the enriched sequences, but also the overall SELEX efficiency and aptamer efficacy. PMID:27652575
A MATHEMATICAL ANALYSIS OF SELEX
Levine, Howard A.; Nilsen-Hamilton, Marit
2007-01-01
SELEX (Systematic Evolution of Ligands by Exponential Enrichment) is a procedure by which a mixture of nucleic acids can be separated into pure components with the goal of isolating those with specific biochemical activities. The basic idea is to combine the mixture with a specific target molecule and then separate the target-NA complex from the resulting reaction. The target-NA complex is then separated by mechanical means (for example by nitrocellulose filtration), the NA is then eluted from the complex, amplified by PCR (polymerase chain reaction) and the process repeated. After several rounds, one should be left with a pool of [NA]that consists mostly of the species in the original pool that best binds to the target. In Irvine et al. (1991) a mathematical analysis of this process was given. In this paper we revisit Irvine et al. (1991). By rewriting the equations for the SELEX process, we considerably reduce the labor of computing the round to round distribution of nucleic acid fractions. We also establish necessary and sufficient conditions for the SELEX process to converge to a pool consisting solely of the best binding nucleic acid to a fixed target in a manner that maximizes the percentage of bound target. The assumption is that there is a single nucleic acid binding site on the target that permits occupation by no more than one nucleic acid. We analyze the case for which there is no background loss, (no support losses and no free [NA] left on the support.) We then examine the case in which such there are such losses. The significance of the analysis is that it suggests an experimental approach for the SELEX process as defined in Irvine et al. (1991) to converge to a pool consisting of a single best binding nucleic acid without recourse to any a-priori information about the nature of the binding constants or the distribution of the individual nucleic acid fragments. PMID:17218151
Whole-bacterium SELEX of DNA aptamers for rapid detection of E.coli O157:H7 using a QCM sensor.
Yu, Xiaofan; Chen, Fang; Wang, Ronghui; Li, Yanbin
2018-01-20
The rapid detection of foodborne pathogens is critical to ensure food safety. The objective of this study is to select aptamers specifically bound to Escherichia coli O157:H7 using the whole-bacterium SELEX (Systematic Evolution of Ligands by Exponential Enrichment) and apply the selected aptamer to a QCM (quartz crystal microbalance) sensor for rapid and sensitive detection of target bacteria. A total of 19 rounds of selection against live E. coli O157:H7 and 6 rounds of counter selection against a mixture of Staphylococcus aureus, Listeria monocytogenes, and Salmonella Typhimurium, were performed. The aptamer pool from the last round was cloned and sequenced. One sequence S1 that appeared 16 times was characterized and a dissociation constant (K d ) of 10.30nM was obtained. Subsequently, a QCM aptasensor was developed for the rapid detection of E. coli O157:H7. The limit of detection (LOD) and the detection time of the aptasensor was determined to be 1.46×10 3 CFU/ml and 50min, respectively. This study demonstrated that the ssDNA aptamer selected by the whole-bacterium SELEX possessed higher sensitivity than previous work and the potential use of the constructed QCM aptasensor in rapid screening of foodborne pathogens. Copyright © 2017 Elsevier B.V. All rights reserved.
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.
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
Development of aptamers against unpurified proteins.
Goto, Shinichi; Tsukakoshi, Kaori; Ikebukuro, Kazunori
2017-12-01
SELEX (Systematic Evolution of Ligands by EXponential enrichment) has been widely used for the generation of aptamers against target proteins. However, its requirement for pure target proteins remains a major problem in aptamer selection, as procedures for protein purification from crude bio-samples are not only complicated but also time and labor consuming. This is because native proteins can be found in a large number of diverse forms because of posttranslational modifications and their complicated molecular conformations. Moreover, several proteins are difficult to purify owing to their chemical fragility and/or rarity in native samples. An alternative route is the use of recombinant proteins for aptamer selection, because they are homogenous and easily purified. However, aptamers generated against recombinant proteins produced in prokaryotic cells may not interact with the same proteins expressed in eukaryotic cells because of posttranslational modifications. Moreover, to date recombinant proteins have been constructed for only a fraction of proteins expressed in the human body. Therefore, the demand for advanced SELEX methods not relying on complicated purification processes from native samples or recombinant proteins is growing. This review article describes several such techniques that allow researchers to directly develop an aptamer from various unpurified samples, such as whole cells, tissues, serum, and cell lysates. The key advantages of advanced SELEX are that it does not require a purification process from a crude bio-sample, maintains the functional states of target proteins, and facilitates the development of aptamers against unidentified and uncharacterized proteins in unpurified biological samples. © 2017 Wiley Periodicals, Inc.
A mathematical analysis of multiple-target SELEX.
Seo, Yeon-Jung; Chen, Shiliang; Nilsen-Hamilton, Marit; Levine, Howard A
2010-10-01
SELEX (Systematic Evolution of Ligands by Exponential Enrichment) is a procedure by which a mixture of nucleic acids can be fractionated with the goal of identifying those with specific biochemical activities. One combines the mixture with a specific target molecule and then separates the target-NA complex from the resulting reactions. The target-NA complex is separated from the unbound NA by mechanical means (such as by filtration), the NA is eluted from the complex, amplified by PCR (polymerase chain reaction), and the process repeated. After several rounds, one should be left with the nucleic acids that best bind to the target. The problem was first formulated mathematically in Irvine et al. (J. Mol. Biol. 222:739-761, 1991). In Levine and Nilsen-Hamilton (Comput. Biol. Chem. 31:11-25, 2007), a mathematical analysis of the process was given. In Vant-Hull et al. (J. Mol. Biol. 278:579-597, 1998), multiple target SELEX was considered. It was assumed that each target has a single nucleic acid binding site that permits occupation by no more than one nucleic acid. Here, we revisit Vant-Hull et al. (J. Mol. Biol. 278:579-597, 1998) using the same assumptions. The iteration scheme is shown to be convergent and a simplified algorithm is given. Our interest here is in the behavior of the multiple target SELEX process as a discrete "time" dynamical system. Our goal is to characterize the limiting states and their dependence on the initial distribution of nucleic acid and target fraction components. (In multiple target SELEX, we vary the target component fractions, but not their concentrations, as fixed and the initial pool of nucleic acids as a variable starting condition). Given N nucleic acids and a target consisting of M subtarget component species, there is an M × N matrix of affinities, the (i,j) entry corresponding to the affinity of the jth nucleic acid for the ith subtarget. We give a structure condition on this matrix that is equivalent to the following statement: For any initial pool of nucleic acids such that all N species are represented, the dynamical system defined by the multiple target SELEX process will converge to a unique subset of nucleic acids, each of whose concentrations depend only upon the total nucleic acid concentration, the initial fractional target distribution (both of which are assumed to be the same from round to round), and the overall limiting association constant. (The overall association constant is the equilibrium constant for the system of MN reactions when viewed as a composite single reaction). This condition is equivalent to the statement that every member of a certain family of chemical potentials at infinite target dilution can have at most one critical point. (The condition replaces the statement for single target SELEX that the dynamical system generated via the process always converges to a pool that contains only the nucleic acid that binds best to the target). This suggests that the effectiveness of multiple target SELEX as a separation procedure may not be as useful as single target SELEX unless the thermodynamic properties of these chemical potentials are well understood.
Lipi, Farhana; Chen, Suxiang; Chakravarthy, Madhuri; Rakesh, Shilpa; Veedu, Rakesh N
2016-12-01
Nucleic acid aptamers are single-stranded DNA or RNA oligonucleotide sequences that bind to a specific target molecule with high affinity and specificity through their ability to adopt 3-dimensional structure in solution. Aptamers have huge potential as targeted therapeutics, diagnostics, delivery agents and as biosensors. However, aptamers composed of natural nucleotide monomers are quickly degraded in vivo and show poor pharmacodynamic properties. To overcome this, chemically-modified nucleic acid aptamers are developed by incorporating modified nucleotides after or during the selection process by Systematic Evolution of Ligands by EXponential enrichment (SELEX). This review will discuss the development of chemically-modified aptamers and provide the pros and cons, and new insights on in vitro aptamer selection strategies by using chemically-modified nucleic acid libraries.
Chen, Suxiang; Chakravarthy, Madhuri; Rakesh, Shilpa; Veedu, Rakesh N.
2016-01-01
ABSTRACT Nucleic acid aptamers are single-stranded DNA or RNA oligonucleotide sequences that bind to a specific target molecule with high affinity and specificity through their ability to adopt 3-dimensional structure in solution. Aptamers have huge potential as targeted therapeutics, diagnostics, delivery agents and as biosensors. However, aptamers composed of natural nucleotide monomers are quickly degraded in vivo and show poor pharmacodynamic properties. To overcome this, chemically-modified nucleic acid aptamers are developed by incorporating modified nucleotides after or during the selection process by Systematic Evolution of Ligands by EXponential enrichment (SELEX). This review will discuss the development of chemically-modified aptamers and provide the pros and cons, and new insights on in vitro aptamer selection strategies by using chemically-modified nucleic acid libraries. PMID:27715478
Label-free detection of gliadin food allergen mediated by real-time apta-PCR.
Pinto, Alessandro; Polo, Pedro Nadal; Henry, Olivier; Redondo, M Carmen Bermudo; Svobodova, Marketa; O'Sullivan, Ciara K
2014-01-01
Celiac disease is an immune-mediated enteropathy triggered by the ingestion of gluten. The only effective treatment consists in a lifelong gluten-free diet, requiring the food industry to tightly control the gluten contents of their products. To date, several gluten quantification approaches using antibodies are available and recommended by the legal authorities, such as Codex Alimentarius. However, whilst these antibody-based tests exhibit high sensitivity and specificity, the production of antibodies inherently requires the killing of host animals and is time-consuming and relatively expensive. Aptamers are structured single-stranded nucleic acid ligands that bind with high affinity and specificity to their cognate target, and aiming for a cost-effective viable alternative to the use of antibodies. Herein, we report the systematic evolution of ligands by exponential enrichment (SELEX)-based selection of a DNA aptamer against gliadin from a combinatorial DNA library and its application in a novel detection assay. Taking into account the hydrophobic nature of the gliadin target, a microtitre plate format was exploited for SELEX, where the target was immobilised via hydrophobic interactions, thus exposing aptatopes accessible for interaction with the DNA library. Evolution was followed using surface plasmon resonance, and following eight rounds of SELEX, the enriched DNA pool was cloned, sequenced and a clear consensus motif was identified. An apta-PCR assay was developed where competition for the aptamer takes place between the surface-immobilised gliadin and gliadin in the target sample, akin to an ELISA competitive format where the more target present in the sample, the less aptamer will bind to the immobilised gliadin. Following competition, any aptamer bound to the immobilised gliadin was heat-eluted and quantitatively amplified using real-time PCR, achieving a detection limit of approx. 2 nM (100 ng mL(-1)). The specificity of the selected aptamer was demonstrated and no cross-reactivity was observed with streptavidin, bovine serum albumin or anti-gliadin IgG.
Rohloff, John C; Gelinas, Amy D; Jarvis, Thale C; Ochsner, Urs A; Schneider, Daniel J; Gold, Larry; Janjic, Nebojsa
2014-01-01
Limited chemical diversity of nucleic acid libraries has long been suspected to be a major constraining factor in the overall success of SELEX (Systematic Evolution of Ligands by EXponential enrichment). Despite this constraint, SELEX has enjoyed considerable success over the past quarter of a century as a result of the enormous size of starting libraries and conformational richness of nucleic acids. With judicious introduction of functional groups absent in natural nucleic acids, the “diversity gap” between nucleic acid–based ligands and protein-based ligands can be substantially bridged, to generate a new class of ligands that represent the best of both worlds. We have explored the effect of various functional groups at the 5-position of uracil and found that hydrophobic aromatic side chains have the most profound influence on the success rate of SELEX and allow the identification of ligands with very low dissociation rate constants (named Slow Off-rate Modified Aptamers or SOMAmers). Such modified nucleotides create unique intramolecular motifs and make direct contacts with proteins. Importantly, SOMAmers engage their protein targets with surfaces that have significantly more hydrophobic character compared with conventional aptamers, thereby increasing the range of epitopes that are available for binding. These improvements have enabled us to build a collection of SOMAmers to over 3,000 human proteins encompassing major families such as growth factors, cytokines, enzymes, hormones, and receptors, with additional SOMAmers aimed at pathogen and rodent proteins. Such a large and growing collection of exquisite affinity reagents expands the scope of possible applications in diagnostics and therapeutics. PMID:25291143
Selection of Aptamers for Mature White Adipocytes by Cell SELEX Using Flow Cytometry
Kim, Eun Young; Kim, Ji Won; Kim, Won Kon; Han, Baek Soo; Park, Sung Goo; Chung, Bong Hyun; Lee, Sang Chul; Bae, Kwang-Hee
2014-01-01
Background Adipose tissue, mainly composed of adipocytes, plays an important role in metabolism by regulating energy homeostasis. Obesity is primarily caused by an abundance of adipose tissue. Therefore, specific targeting of adipose tissue is critical during the treatment of obesity, and plays a major role in overcoming it. However, the knowledge of cell-surface markers specific to adipocytes is limited. Methods and Results We applied the CELL SELEX (Systematic Evolution of Ligands by EXponential enrichment) method using flow cytometry to isolate molecular probes for specific recognition of adipocytes. The aptamer library, a mixture of FITC-tagged single-stranded random DNAs, is used as a source for acquiring molecular probes. With the increasing number of selection cycles, there was a steady increase in the fluorescence intensity toward mature adipocytes. Through 12 rounds of SELEX, enriched aptamers showing specific recognition toward mature 3T3-L1 adipocyte cells were isolated. Among these, two aptamers (MA-33 and 91) were able to selectively bind to mature adipocytes with an equilibrium dissociation constant (Kd) in the nanomolar range. These aptamers did not bind to preadipocytes or other cell lines (such as HeLa, HEK-293, or C2C12 cells). Additionally, it was confirmed that MA-33 and 91 can distinguish between mature primary white and primary brown adipocytes. Conclusions These selected aptamers have the potential to be applied as markers for detecting mature white adipocytes and monitoring adipogenesis, and could emerge as an important tool in the treatment of obesity. PMID:24844710
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.
Zhang, Wei Yun; Zhang, Wenhua; Liu, Zhiyuan; Li, Cong; Zhu, Zhi; Yang, Chaoyong James
2012-01-03
We have developed a novel method for efficiently screening affinity ligands (aptamers) from a complex single-stranded DNA (ssDNA) library by employing single-molecule emulsion polymerase chain reaction (PCR) based on the agarose droplet microfluidic technology. In a typical systematic evolution of ligands by exponential enrichment (SELEX) process, the enriched library is sequenced first, and tens to hundreds of aptamer candidates are analyzed via a bioinformatic approach. Possible candidates are then chemically synthesized, and their binding affinities are measured individually. Such a process is time-consuming, labor-intensive, inefficient, and expensive. To address these problems, we have developed a highly efficient single-molecule approach for aptamer screening using our agarose droplet microfluidic technology. Statistically diluted ssDNA of the pre-enriched library evolved through conventional SELEX against cancer biomarker Shp2 protein was encapsulated into individual uniform agarose droplets for droplet PCR to generate clonal agarose beads. The binding capacity of amplified ssDNA from each clonal bead was then screened via high-throughput fluorescence cytometry. DNA clones with high binding capacity and low K(d) were chosen as the aptamer and can be directly used for downstream biomedical applications. We have identified an ssDNA aptamer that selectively recognizes Shp2 with a K(d) of 24.9 nM. Compared to a conventional sequencing-chemical synthesis-screening work flow, our approach avoids large-scale DNA sequencing and expensive, time-consuming DNA synthesis of large populations of DNA candidates. The agarose droplet microfluidic approach is thus highly efficient and cost-effective for molecular evolution approaches and will find wide application in molecular evolution technologies, including mRNA display, phage display, and so on. © 2011 American Chemical Society
Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems.
Jiang, Feng; Liu, Biao; Lu, Jun; Li, Fangfei; Li, Defang; Liang, Chao; Dang, Lei; Liu, Jin; He, Bing; Badshah, Shaikh Atik; Lu, Cheng; He, Xiaojuan; Guo, Baosheng; Zhang, Xiao-Bing; Tan, Weihong; Lu, Aiping; Zhang, Ge
2015-10-09
Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems.
In vitro Selection and Interaction Studies of a DNA Aptamer Targeting Protein A
Stoltenburg, Regina; Schubert, Thomas; Strehlitz, Beate
2015-01-01
A new DNA aptamer targeting Protein A is presented. The aptamer was selected by use of the FluMag-SELEX procedure. The SELEX technology (Systematic Evolution of Ligands by EXponential enrichment) is widely applied as an in vitro selection and amplification method to generate target-specific aptamers and exists in various modified variants. FluMag-SELEX is one of them and is characterized by the use of magnetic beads for target immobilization and fluorescently labeled oligonucleotides for monitoring the aptamer selection progress. Structural investigations and sequence truncation experiments of the selected aptamer for Protein A led to the conclusion, that a stem-loop structure at its 5’-end including the 5’-primer binding site is essential for aptamer-target binding. Extensive interaction analyses between aptamer and Protein A were performed by methods like surface plasmon resonance, MicroScale Thermophoresis and bead-based binding assays using fluorescence measurements. The binding of the aptamer to its target was thus investigated in assays with immobilization of one of the binding partners each, and with both binding partners in solution. Affinity constants were determined in the low micromolar to submicromolar range, increasing to the nanomolar range under the assumption of avidity. Protein A provides more than one binding site for the aptamer, which may overlap with the known binding sites for immunoglobulins. The aptamer binds specifically to both native and recombinant Protein A, but not to other immunoglobulin-binding proteins like Protein G and L. Cross specificity to other proteins was not found. The application of the aptamer is directed to Protein A detection or affinity purification. Moreover, whole cells of Staphylococcus aureus, presenting Protein A on the cell surface, could also be bound by the aptamer. PMID:26221730
In vitro Selection and Interaction Studies of a DNA Aptamer Targeting Protein A.
Stoltenburg, Regina; Schubert, Thomas; Strehlitz, Beate
2015-01-01
A new DNA aptamer targeting Protein A is presented. The aptamer was selected by use of the FluMag-SELEX procedure. The SELEX technology (Systematic Evolution of Ligands by EXponential enrichment) is widely applied as an in vitro selection and amplification method to generate target-specific aptamers and exists in various modified variants. FluMag-SELEX is one of them and is characterized by the use of magnetic beads for target immobilization and fluorescently labeled oligonucleotides for monitoring the aptamer selection progress. Structural investigations and sequence truncation experiments of the selected aptamer for Protein A led to the conclusion, that a stem-loop structure at its 5'-end including the 5'-primer binding site is essential for aptamer-target binding. Extensive interaction analyses between aptamer and Protein A were performed by methods like surface plasmon resonance, MicroScale Thermophoresis and bead-based binding assays using fluorescence measurements. The binding of the aptamer to its target was thus investigated in assays with immobilization of one of the binding partners each, and with both binding partners in solution. Affinity constants were determined in the low micromolar to submicromolar range, increasing to the nanomolar range under the assumption of avidity. Protein A provides more than one binding site for the aptamer, which may overlap with the known binding sites for immunoglobulins. The aptamer binds specifically to both native and recombinant Protein A, but not to other immunoglobulin-binding proteins like Protein G and L. Cross specificity to other proteins was not found. The application of the aptamer is directed to Protein A detection or affinity purification. Moreover, whole cells of Staphylococcus aureus, presenting Protein A on the cell surface, could also be bound by the aptamer.
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.
Smaczniak, Cezary; Muiño, Jose M; Chen, Dijun; Angenent, Gerco C; Kaufmann, Kerstin
2017-08-01
Floral organ identities in plants are specified by the combinatorial action of homeotic master regulatory transcription factors. However, how these factors achieve their regulatory specificities is still largely unclear. Genome-wide in vivo DNA binding data show that homeotic MADS domain proteins recognize partly distinct genomic regions, suggesting that DNA binding specificity contributes to functional differences of homeotic protein complexes. We used in vitro systematic evolution of ligands by exponential enrichment followed by high-throughput DNA sequencing (SELEX-seq) on several floral MADS domain protein homo- and heterodimers to measure their DNA binding specificities. We show that specification of reproductive organs is associated with distinct binding preferences of a complex formed by SEPALLATA3 and AGAMOUS. Binding specificity is further modulated by different binding site spacing preferences. Combination of SELEX-seq and genome-wide DNA binding data allows differentiation between targets in specification of reproductive versus perianth organs in the flower. We validate the importance of DNA binding specificity for organ-specific gene regulation by modulating promoter activity through targeted mutagenesis. Our study shows that intrafamily protein interactions affect DNA binding specificity of floral MADS domain proteins. Differential DNA binding of MADS domain protein complexes plays a role in the specificity of target gene regulation. © 2017 American Society of Plant Biologists. All rights reserved.
In vitro selection using a dual RNA library that allows primerless selection
Jarosch, Florian; Buchner, Klaus; Klussmann, Sven
2006-01-01
High affinity target-binding aptamers are identified from random oligonucleotide libraries by an in vitro selection process called Systematic Evolution of Ligands by EXponential enrichment (SELEX). Since the SELEX process includes a PCR amplification step the randomized region of the oligonucleotide libraries need to be flanked by two fixed primer binding sequences. These primer binding sites are often difficult to truncate because they may be necessary to maintain the structure of the aptamer or may even be part of the target binding motif. We designed a novel type of RNA library that carries fixed sequences which constrain the oligonucleotides into a partly double-stranded structure, thereby minimizing the risk that the primer binding sequences become part of the target-binding motif. Moreover, the specific design of the library including the use of tandem RNA Polymerase promoters allows the selection of oligonucleotides without any primer binding sequences. The library was used to select aptamers to the mirror-image peptide of ghrelin. Ghrelin is a potent stimulator of growth-hormone release and food intake. After selection, the identified aptamer sequences were directly synthesized in their mirror-image configuration. The final 44 nt-Spiegelmer, named NOX-B11-3, blocks ghrelin action in a cell culture assay displaying an IC50 of 4.5 nM at 37°C. PMID:16855281
Hamula, Camille L A; Peng, Hanyong; Wang, Zhixin; Tyrrell, Gregory J; Li, Xing-Fang; Le, X Chris
2016-03-15
Streptococcus pyogenes is a clinically important pathogen consisting of various serotypes determined by different M proteins expressed on the cell surface. The M type is therefore a useful marker to monitor the spread of invasive S. pyogenes in a population. Serotyping and nucleic acid amplification/sequencing methods for the identification of M types are laborious, inconsistent, and usually confined to reference laboratories. The primary objective of this work is to develop a technique that enables generation of aptamers binding to specific M-types of S. pyogenes. We describe here an in vitro technique that directly used live bacterial cells and the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) strategy. Live S. pyogenes cells were incubated with DNA libraries consisting of 40-nucleotides randomized sequences. Those sequences that bound to the cells were separated, amplified using polymerase chain reaction (PCR), purified using gel electrophoresis, and served as the input DNA pool for the next round of SELEX selection. A specially designed forward primer containing extended polyA20/5Sp9 facilitated gel electrophoresis purification of ssDNA after PCR amplification. A counter-selection step using non-target cells was introduced to improve selectivity. DNA libraries of different starting sequence diversity (10(16) and 10(14)) were compared. Aptamer pools from each round of selection were tested for their binding to the target and non-target cells using flow cytometry. Selected aptamer pools were then cloned and sequenced. Individual aptamer sequences were screened on the basis of their binding to the 10 M-types that were used as targets. Aptamer pools obtained from SELEX rounds 5-8 showed high affinity to the target S. pyogenes cells. Tests against non-target Streptococcus bovis, Streptococcus pneumoniae, and Enterococcus species demonstrated selectivity of these aptamers for binding to S. pyogenes. Several aptamer sequences were found to bind preferentially to the M11 M-type of S. pyogenes. Estimated binding dissociation constants (Kd) were in the low nanomolar range for the M11 specific sequences; for example, sequence E-CA20 had a Kd of 7±1 nM. These affinities are comparable to those of a monoclonal antibody. The improved bacterial cell-SELEX technique is successful in generating aptamers selective for S. pyogenes and some of its M-types. These aptamers are potentially useful for detecting S. pyogenes, achieving binding profiles of the various M-types, and developing new M-typing technologies for non-specialized laboratories or point-of-care testing. Copyright © 2015 Elsevier Inc. All rights reserved.
Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems
Jiang, Feng; Liu, Biao; Lu, Jun; Li, Fangfei; Li, Defang; Liang, Chao; Dang, Lei; Liu, Jin; He, Bing; Atik Badshah, Shaikh; Lu, Cheng; He, Xiaojuan; Guo, Baosheng; Zhang, Xiao-Bing; Tan, Weihong; Lu, Aiping; Zhang, Ge
2015-01-01
Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems. PMID:26473828
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.
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
Development of an aptamer-conjugated fluorescent nanoprobe for MMP2
NASA Astrophysics Data System (ADS)
Han, Myoung-Eun; Baek, Sungmin; Kim, Hyun-Jung; Lee, Jung Hwan; Ryu, Sung-Ho; Oh, Sae-Ock
2014-03-01
Matrix metalloproteinase 2 (MMP2) plays critical roles in various diseases, such as atherosclerosis and cancer, and has been suggested to contribute to the instability of atherosclerotic plaque. To visualize MMP2 in pathologic tissues, we developed an aptamer targeting MMP2 protein by performing eight rounds of modified DNA systematic evolution of ligands by exponential enrichment (SELEX). The aptamer showed high affinity for MMP2 ( K d = 5.59 nM), precipitated MMP2, and detected MMP2 protein in pathological tissues such as atherosclerotic plaque and gastric cancer tissues. Furthermore, a MMP2 aptamer-conjugated fluorescent nanoprobe successfully visualized atherosclerotic plaques in apolipoprotein E (ApoE) knockout mice. These results suggest that the devised MMP2 aptamer could be useful for the development of various diagnostic tools.
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.
Sedighian, Hamid; Halabian, Raheleh; Amani, Jafar; Heiat, Mohammad; Taheri, Ramezan Ali; Imani Fooladi, Abbas Ali
2018-05-01
Staphylococcal enterotoxin A (SEA) is an enterotoxin produced mainly by Staphylococcus aureus. In recent years, it has become the most prevalent compound for staphylococcal food poisoning (SFP) around the world. In this study, we isolate new dual-function single-stranded DNA (ssDNA) aptamers by using some new methods, such as the Taguchi method, by focusing on the detection and neutralization of SEA enterotoxin in food and clinical samples. For the asymmetric polymerase chain reaction (PCR) optimization of each round of systematic evolution of ligands by exponential enrichment (SELEX), we use Taguchi L9 orthogonal arrays, and the aptamer mobility shift assay (AMSA) is used for initial evaluation of the protein-DNA interactions on the last SELEX round. In our investigation the dissociation constant (K D ) value and the limit of detection (LOD) of the candidate aptamer were found to be 8.5 ± 0.91 of nM and 5 ng/ml using surface plasmon resonance (SPR). In the current study, the Taguchi and mobility shift assay methods were innovatively harnessed to improve the selection process and evaluate the protein-aptamer interactions. To the best of our knowledge, this is the first report on employing these two methods in aptamer technology especially against bacterial toxin. Copyright © 2018 Elsevier Inc. All rights reserved.
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
Primer-Free Aptamer Selection Using A Random DNA Library
Pan, Weihua; Xin, Ping; Patrick, Susan; Dean, Stacey; Keating, Christine; Clawson, Gary
2010-01-01
Aptamers are highly structured oligonucleotides (DNA or RNA) that can bind to targets with affinities comparable to antibodies 1. They are identified through an in vitro selection process called Systematic Evolution of Ligands by EXponential enrichment (SELEX) to recognize a wide variety of targets, from small molecules to proteins and other macromolecules 2-4. Aptamers have properties that are well suited for in vivo diagnostic and/or therapeutic applications: Besides good specificity and affinity, they are easily synthesized, survive more rigorous processing conditions, they are poorly immunogenic, and their relatively small size can result in facile penetration of tissues. Aptamers that are identified through the standard SELEX process usually comprise ~80 nucleotides (nt), since they are typically selected from nucleic acid libraries with ~40 nt long randomized regions plus fixed primer sites of ~20 nt on each side. The fixed primer sequences thus can comprise nearly ~50% of the library sequences, and therefore may positively or negatively compromise identification of aptamers in the selection process 3, although bioinformatics approaches suggest that the fixed sequences do not contribute significantly to aptamer structure after selection 5. To address these potential problems, primer sequences have been blocked by complementary oligonucleotides or switched to different sequences midway during the rounds of SELEX 6, or they have been trimmed to 6-9 nt 7, 8. Wen and Gray 9 designed a primer-free genomic SELEX method, in which the primer sequences were completely removed from the library before selection and were then regenerated to allow amplification of the selected genomic fragments. However, to employ the technique, a unique genomic library has to be constructed, which possesses limited diversity, and regeneration after rounds of selection relies on a linear reamplification step. Alternatively, efforts to circumvent problems caused by fixed primer sequences using high efficiency partitioning are met with problems regarding PCR amplification 10. We have developed a primer-free (PF) selection method that significantly simplifies SELEX procedures and effectively eliminates primer-interference problems 11, 12. The protocols work in a straightforward manner. The central random region of the library is purified without extraneous flanking sequences and is bound to a suitable target (for example to a purified protein or complex mixtures such as cell lines). Then the bound sequences are obtained, reunited with flanking sequences, and re-amplified to generate selected sub-libraries. As an example, here we selected aptamers to S100B, a protein marker for melanoma. Binding assays showed Kd s in the 10-7 - 10-8 M range after a few rounds of selection, and we demonstrate that the aptamers function effectively in a sandwich binding format. PMID:20689511
Aptamer-integrated DNA nanostructures for biosensing, bioimaging and cancer therapy.
Meng, Hong-Min; Liu, Hui; Kuai, Hailan; Peng, Ruizi; Mo, Liuting; Zhang, Xiao-Bing
2016-05-03
The combination of nanostructures with biomolecules leading to the generation of functional nanosystems holds great promise for biotechnological and biomedical applications. As a naturally occurring biomacromolecule, DNA exhibits excellent biocompatibility and programmability. Also, scalable synthesis can be readily realized through automated instruments. Such unique properties, together with Watson-Crick base-pairing interactions, make DNA a particularly promising candidate to be used as a building block material for a wide variety of nanostructures. In the past few decades, various DNA nanostructures have been developed, including one-, two- and three-dimensional nanomaterials. Aptamers are single-stranded DNA or RNA molecules selected by Systematic Evolution of Ligands by Exponential Enrichment (SELEX), with specific recognition abilities to their targets. Therefore, integrating aptamers into DNA nanostructures results in powerful tools for biosensing and bioimaging applications. Furthermore, owing to their high loading capability, aptamer-modified DNA nanostructures have also been altered to play the role of drug nanocarriers for in vivo applications and targeted cancer therapy. In this review, we summarize recent progress in the design of aptamers and related DNA molecule-integrated DNA nanostructures as well as their applications in biosensing, bioimaging and cancer therapy. To begin with, we first introduce the SELEX technology. Subsequently, the methodologies for the preparation of aptamer-integrated DNA nanostructures are presented. Then, we highlight their applications in biosensing and bioimaging for various targets, as well as targeted cancer therapy applications. Finally, we discuss several challenges and further opportunities in this emerging field.
Aptamer-based surface plasmon resonance sensing of glycated human blood proteins
NASA Astrophysics Data System (ADS)
Reaver, Nathan G. F.; Zheng, Rui; Kim, Dong-Shik; Cameron, Brent D.
2013-02-01
The concentration ratio of glycated to non-glycated forms of various blood proteins can be used as a diagnostic measure in diabetes to determine a history of glycemic compliance. Depending on a protein's half-life in blood, compliance can be assessed from a few days to several months in the past, which can then be used to provide additional therapeutic guidance. Current glycated protein detection methods are limited in their ability to measure multiple proteins, and are susceptible to interference from other blood pathologies. In this study, we developed and characterized DNA aptamers for use in Surface Plasmon Resonance (SPR) sensors to assess the blood protein hemoglobin. The aptamers were developed by way of a modified Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process which selects DNA sequences that have a high binding affinity to a specific protein. DNA products resulting from this process are sequenced and identified aptamers are then synthesized. The SELEX process was performed to produce aptamers for a glycated form of hemoglobin. Equilibrium dissociation constants for the binding of the identified aptamer to glycated hemoglobin, hemoglobin, and fibrinogen were calculated from fitted Langmuir isotherms obtained through SPR. These constants were determined to be 94 nM, 147 nM, and 244 nM respectively. This aptamer can potentially be used to create a SPR aptamer based biosensor for detection of glycated hemoglobin, a technology that has the potential to deliver low-cost and immediate glycemic compliance assessment in either a clinical or home setting.
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
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.
Recent progresses in biomedical applications of aptamer-functionalized systems.
Ding, Fei; Gao, Yangguang; He, Xianran
2017-09-15
Aptamers, known as "chemical antibodies" are screened via a combinational technology of systematic evolution of ligands by exponential enrichment (SELEX). Due to their specific targeting ability, high binding affinity, low immunogenicity and easy modification, aptamer-functionalized systems have been extensively applied in various fields and exhibit favorable results. However, there is still a long way for them to be commercialized, and few aptamer-functionalized systems have yet successfully entered clinical and industrial use. Thus, it is necessary to overview the recent research progresses of aptamer-functionalized systems for the researchers to improve or design novel and better aptamer-functionalized systems. In this review, we first introduce the recent progresses of aptamer-functionalized systems' applications in biosensing, targeted drug delivery, gene therapy and cancer cell imaging, followed by a discussion of the challenges faced with extensive applications of aptamer-functionalized systems and speculation of the future prospects of them. Copyright © 2017 Elsevier Ltd. All rights reserved.
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.
Replacing antibodies with aptamers in lateral flow immunoassay.
Chen, Ailiang; Yang, Shuming
2015-09-15
Aptamers have been identified against various targets as a type of chemical or nucleic acid ligand by systematic evolution of ligands by exponential enrichment (SELEX) with high sensitivity and specificity. Aptamers show remarkable advantages over antibodies due to the nucleic acid nature and target-induced structure-switching properties and are widely used to design various fluorescent, electrochemical, or colorimetric biosensors. However, the practical applications of aptamer-based sensing and diagnostics are still lagging behind those of antibody-based tests. Lateral flow immunoassay (LFIA) represents a well established and appropriate technology among rapid assays because of its low cost and user-friendliness. The antibody-based platform is utilized to detect numerous targets, but it is always hampered by the antibody preparation time, antibody stability, and effect of modification on the antibody. Seeking alternatives to antibodies is an area of active research and is of tremendous importance. Aptamers are receiving increasing attention in lateral flow applications because of a number of important potential performance advantages. We speculate that aptamer-based LFIA may be one of the first platforms for commercial use of aptamer-based diagnosis. This review first gives an introduction to aptamer including the selection process SELEX with its focus on aptamer advantages over antibodies, and then depicts LFIA with its focus on aptamer opportunities in LFIA over antibodies. Furthermore, we summarize the recent advances in the development of aptamer-based lateral flow biosensing assays with the aim to provide a general guide for the design of aptamer-based lateral flow biosensing assays. Copyright © 2015 Elsevier B.V. All rights reserved.
Dimeric PROP1 binding to diverse palindromic TAAT sequences promotes its transcriptional activity.
Nakayama, Michie; Kato, Takako; Susa, Takao; Sano, Akiko; Kitahara, Kousuke; Kato, Yukio
2009-08-13
Mutations in the Prop1 gene are responsible for murine Ames dwarfism and human combined pituitary hormone deficiency with hypogonadism. Recently, we reported that PROP1 is a possible transcription factor for gonadotropin subunit genes through plural cis-acting sites composed of AT-rich sequences containing a TAAT motif which differs from its consensus binding sequence known as PRDQ9 (TAATTGAATTA). This study aimed to verify the binding specificity and sequence of PROP1 by applying the method of SELEX (Systematic Evolution of Ligands by EXponential enrichment), EMSA (electrophoretic mobility shift assay) and transient transfection assay. SELEX, after 5, 7 and 9 generations of selection using a random sequence library, showed that nucleotides containing one or two TAAT motifs were accumulated and accounted for 98.5% at the 9th generation. Aligned sequences and EMSA demonstrated that PROP1 binds preferentially to 11 nucleotides composed of an inverted TAAT motif separated by 3 nucleotides with variation in the half site of palindromic TAAT motifs and with preferential requirement of T at the nucleotide number 5 immediately 3' to a TAAT motif. Transient transfection assay demonstrated first that dimeric binding of PROP1 to an inverted TAAT motif and its cognates resulted in transcriptional activation, whereas monomeric binding of PROP1 to a single TAAT motif and an inverted ATTA motif did not mediate activation. Thus, this study demonstrated that dimeric binding of PROP1 is able to recognize diverse palindromic TAAT sequences separated by 3 nucleotides and to exhibit its transcriptional activity.
Structural Plasticity and Rapid Evolution in a Viral RNA Revealed by In Vivo Genetic Selection▿ †
Guo, Rong; Lin, Wai; Zhang, Jiuchun; Simon, Anne E.; Kushner, David B.
2009-01-01
Satellite RNAs usually lack substantial homology with their helper viruses. The 356-nucleotide satC of Turnip crinkle virus (TCV) is unusual in that its 3′-half shares high sequence similarity with the TCV 3′ end. Computer modeling, structure probing, and/or compensatory mutagenesis identified four hairpins and three pseudoknots in this TCV region that participate in replication and/or translation. Two hairpins and two pseudoknots have been confirmed as important for satC replication. One portion of the related 3′ end of satC that remains poorly characterized corresponds to juxtaposed TCV hairpins H4a and H4b and pseudoknot ψ3, which are required for the TCV-specific requirement of translation (V. A. Stupina et al., RNA 14:2379-2393, 2008). Replacement of satC H4a with randomized sequence and scoring for fitness in plants by in vivo genetic selection (SELEX) resulted in winning sequences that contain an H4a-like stem-loop, which can have additional upstream sequence composing a portion of the stem. SELEX of the combined H4a and H4b region in satC generated three distinct groups of winning sequences. One group models into two stem-loops similar to H4a and H4b of TCV. However, the selected sequences in the other two groups model into single hairpins. Evolution of these single-hairpin SELEX winners in plants resulted in satC that can accumulate to wild-type (wt) levels in protoplasts but remain less fit in planta when competed against wt satC. These data indicate that two highly distinct RNA conformations in the H4a and H4b region can mediate satC fitness in protoplasts. PMID:19004956
Selection and identification of a DNA aptamer targeted to Vibrio parahemolyticus.
Duan, Nuo; Wu, Shijia; Chen, Xiujuan; Huang, Yukun; Wang, Zhouping
2012-04-25
A whole-bacterium systemic evolution of ligands by exponential enrichment (SELEX) method was applied to a combinatorial library of FAM-labeled single-stranded DNA molecules to identify DNA aptamers demonstrating specific binding to Vibrio parahemolyticus . FAM-labeled aptamer sequences with high binding affinity to V. parahemolyticus were identified by flow cytometric analysis. Aptamer A3P, which showed a particularly high binding affinity in preliminary studies, was chosen for further characterization. This aptamer displayed a dissociation constant (K(d)) of 16.88 ± 1.92 nM. Binding assays to assess the specificity of aptamer A3P showed a high binding affinity (76%) for V. parahemolyticus and a low apparent binding affinity (4%) for other bacteria. Whole-bacterium SELEX is a promising technique for the design of aptamer-based molecular probes for microbial pathogens that does not require the labor-intensive steps of isolating and purifying complex markers or targets.
Wu, Hang; Mao, Yongrong; Chen, Meng; Pan, Hui; Huang, Xunduan; Ren, Min; Wu, Hao; Li, Jiali; Xu, Zhongdong; Yuan, Hualing; Geng, Ming; Weaver, David T; Zhang, Lixin; Zhang, Buchang
2015-03-01
BldD (SACE_2077), a key developmental regulator in actinomycetes, is the first identified transcriptional factor in Saccharopolyspora erythraea positively regulating erythromycin production and morphological differentiation. Although the BldD of S. erythraea binds to the promoters of erythromycin biosynthetic genes, the interaction affinities are relatively low, implying the existence of its other target genes in S. erythraea. Through the genomic systematic evolution of ligands by exponential enrichment (SELEX) method that we herein improved, four DNA sequences of S. erythraea A226, corresponding to the promoter regions of SACE_0306 (beta-galactosidase), SACE_0811 (50S ribosomal protein L25), SACE_3410 (fumarylacetoacetate hydrolase), and SACE_6014 (aldehyde dehydrogenase), were captured with all three BldD concentrations of 0.5, 1, and 2 μM, while the previously identified intergenic regions of eryBIV-eryAI and ermE-eryCI plus the promoter region of SACE_7115, the amfC homolog for aerial mycelium formation, could be captured only when the BldD's concentration reached 2 μM. Electrophoretic mobility shift assay (EMSA) analysis indicated that BldD specifically bound to above seven DNA sequences, and quantitative real-time PCR (qRT-PCR) assay showed that the transcriptional levels of the abovementioned target genes decreased when bldD was disrupted in A226. Furthermore, SACE_7115 and SACE_0306 in A226 were individually inactivated, showing that SACE_7115 was predominantly involved in aerial mycelium formation, while SACE_0306 mainly controlled erythromycin production. This study provides valuable information for better understanding of the pleiotropic regulator BldD in S. erythraea, and the improved method may be useful for uncovering regulatory networks of other transcriptional factors.
Cui, Wei; Liu, Jiaojiao; Su, Donghua; Hu, Danyang; Hou, Shuai; Hu, Tongnan; Yang, Jiyong; Luo, Yanping; Xi, Qing; Chu, Bingfeng; Wang, Chenglong
2016-06-01
Streptococcus mutans, a Gram-positive facultative anaerobic bacterium, is considered to be a major etiological factor for dental caries. In this study, plaques from dental enamel surfaces of caries-active and caries-free individuals were obtained and cultivated for S. mutans isolation. Morphology examination, biochemical characterization, and polymerase chain reaction were performed to identify S. mutans The cariogenicity of S. mutans strains isolated from clinical specimens was evaluated by testing the acidogenicity, aciduricity, extracellular polysaccharide production, and adhesion ability of the bacteria. Finally, subtractive SELEX (systematic evolution of ligands by exponential enrichment) technology targeting whole intact cells was used to screen for ssDNA aptamers specific to the strains with high cariogenicity. After nine rounds of subtractive SELEX, sufficient pool enrichment was achieved as shown by radioactive isotope analysis. The enriched pool was cloned and sequenced randomly, followed by MEME online and RNA structure software analysis of the sequences. Results from the flow cytometry indicated that aptamers H1, H16, H4, L1, L10, and H19 could discriminate highly cariogenic S. mutans strains from poorly cariogenic strains. Among these, Aptamer H19 had the strongest binding capacity with cariogenic S. mutans strains with a dissociation constant of 69.45 ± 38.53 nM. In conclusion, ssDNA aptamers specific to highly cariogenic clinical S. mutans strains were successfully obtained. These ssDNA aptamers might be used for the early diagnosis and treatment of dental caries. © The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Sooter, Letha J.
2017-01-01
Fipronil is a commonly used insecticide that has been shown to have environmental and human health risks. The current standard methods of detection for fipronil and its metabolites, such as GC-MS, are time consuming and labor intensive. In this study, a variant of systematic evolution of ligands by exponential enrichment (SELEX), was utilized to identify the first single-stranded DNA (ssDNA) molecular recognition element (MRE) that binds to fipronil with high affinity (Kd = 48 ± 8 nM). The selected MRE displayed low cross binding activity on various environmentally relevant, structurally unrelated herbicides and pesticides, in addition to broad-spectrum binding activity on major metabolites of fipronil and a structurally similar pesticide in prepared river samples. Additionally, a proof-of-principle fluorescent detection assay was developed by using the selected ssDNA MRE as a signal-reporting element, with a limit of detection of 105 nM in a prepared river water sample. PMID:29283416
Hünniger, Tim; Fischer, Christin; Wessels, Hauke; Hoffmann, Antonia; Paschke-Kratzin, Angelika; Haase, Ilka; Fischer, Markus
2015-03-04
The quality of the beverage industry's products has to be constantly monitored to fulfill consumers' high expectations. The thermo-acidophilic Gram-positive Alicyclobacillus spp. are not pathogenic, but their heat-resistant endospores can survive juice-processing conditions and have become a major economic concern for the fruit juice industry. Current detection methods rely on cultivation, isolation, and organism identification, which can take up to a week, resulting in economic loss. This work presents the selection and identification of DNA aptamers targeting Alicyclobacillus spores by spore-SELEX (systematic evolution of ligands by exponential enrichment) in orange-juice-simulating buffer. The selection process was verified by various techniques, including flow cytometric binding assays, radioactive binding assays, and agarose gel electrophoresis. The subsequent aptamer characterization included the determination of dissociations constants and selectivity by different techniques, such as surface plasmon resonance spectroscopy and fluorescence microscopy. In summary, 10 different aptamers with an affinity to Alicyclobacillus spp. have been developed, analyzed, and characterized in terms of affinity and specificity.
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.
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
Dolati, Somayeh; Ramezani, Mohammad; Nabavinia, Maryam Sadat; Soheili, Vahid; Abnous, Khalil; Taghdisi, Seyed Mohammad
2018-05-15
Specific ssDNA aptamers for the antibiotic enrofloxacin (ENR) were isolated from an enriched nucleotide library by SELEX (Systematic Evolution of Ligands by EXponential enrichment) method with high binding affinity. After seven rounds, five aptamers were selected and identified. Apt58 with highest affinity and sensitivity (K d = 14.19 nM) was employed to develop a label-free fluorescent biosensing approach based on aptamer, graphene oxide (GO) and native fluorescence of ENR for determination of ENR residue in raw milk samples. Under optimized experimental conditions, the linear range was from 5 nM to 250 nM and LOD was calculated to be 3.7 nM, and the recovery rate was between 94.1% and 108.5%. The integration of aptamer and GO in this bioassay provides a promising way for rapid, sensitive and cost-effective detection of ENR in real samples like raw milk. Copyright © 2018 Elsevier Inc. All rights reserved.
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
Operation and performance of new NIR detectors from SELEX
NASA Astrophysics Data System (ADS)
Atkinson, D.; Bezawada, N.; Hipwood, L. G.; Shorrocks, N.; Milne, H.
2012-07-01
The European Space Agency (ESA) has funded SELEX Galileo, Southampton, UK to develop large format near infrared (NIR) detectors for its future space and ground based programmes. The UKATC has worked in collaboration with SELEX Galileo to test and characterise the new detectors produced during phase-1 of the development. In order to demonstrate the detector material performance, the HgCdTe (MCT) detector diodes (grown on GaAs substrate through MOVPE process in small 320×256, 24μm pixel format) are hybridised to the existing SELEX Galileo SWALLOW CMOS readout chip. The substrate removed and MCT thinned detector arrays were then tested and evaluated at the UKATC following screening tests at SELEX. This paper briefly describes the test setup, the operational aspects of the readout multiplexer and presents the performance parameters of the detector arrays including: conversion gain, detector dark current, read noise, linearity, quantum efficiency and persistence for various detector temperatures between 80K and 140K.
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
Hong, Ka L; Battistella, Luisa; Salva, Alysia D; Williams, Ryan M; Sooter, Letha J
2015-01-27
Alpha toxin is one of the major virulence factors secreted by Staphylococcus aureus, a bacterium that is responsible for a wide variety of infections in both community and hospital settings. Due to the prevalence of S. aureus related infections and the emergence of methicillin-resistant S. aureus, rapid and accurate diagnosis of S. aureus infections is crucial in benefiting patient health outcomes. In this study, a rigorous Systematic Evolution of Ligands by Exponential Enrichment (SELEX) variant previously developed by our laboratory was utilized to select a single-stranded DNA molecular recognition element (MRE) targeting alpha toxin with high affinity and specificity. At the end of the 12-round selection, the selected MRE had an equilibrium dissociation constant (Kd) of 93.7 ± 7.0 nM. Additionally, a modified sandwich enzyme-linked immunosorbent assay (ELISA) was developed by using the selected ssDNA MRE as the toxin-capturing element and a sensitive detection of 200 nM alpha toxin in undiluted human serum samples was achieved.
Affinity Pulldown of Biotinylated RNA for Detection of Protein-RNA Complexes.
Panda, Amaresh C; Martindale, Jennifer L; Gorospe, Myriam
2016-12-20
RNA-binding proteins (RBPs) have recently emerged as crucial players in the regulation of gene expression. The interactions of RBPs with target mRNAs control the levels of gene products by altering different regulatory steps, including pre-mRNA splicing and maturation, nuclear mRNA export, and mRNA stability and translation (Glisovic et al. , 2008). There are several methodologies available today to identify RNAs bound to specific RBPs; some detect only recombinant molecules in vitro , others detect recombinant and endogenous molecules, while others detect only endogenous molecules. Examples include systematic evolution of ligands by exponential enrichment (SELEX), biotinylated RNA pulldown assay, RNA immunoprecipitation (RIP) assay, electrophoretic mobility shift assay (EMSA), RNA footprinting analysis, and various UV crosslinking and immunoprecipitation (CLIP) methods such as CLIP, PAR-CLIP, and iCLIP (Popova et al. , 2015). Here, we describe a simple and informative method to study and identify the RNA region of interaction between an RBP and its target transcript (Panda et al. , 2014 and 2016). Its reproducibility and ease of use make this protocol a fast and useful method to identify interactions between RBPs and specific RNAs.
NASA Astrophysics Data System (ADS)
Orito, N.; Umekage, S.; Sato, K.; Kawauchi, S.; Tanaka, H.; Sakai, E.; Tanaka, T.; Kikuchi, Y.
2012-03-01
We have developed a modified SELEX (systematic evolution of ligands by exponential enrichment) method to obtain RNA aptamers with high affinity to C-reactive protein (CRP). CRP is a clinical biomarker present in plasma, the level of which increases in response to infections and noninfectious inflammation. The CRP level is also an important prognostic indicator in patients with several syndromes. At present, CRP content in blood is measured immunochemically using antibodies. To develop a more sensitive method using RNA aptamers, we have attempted to obtain high-affinity RNA aptamers to CRP. We succeeded in obtaining an RNA aptamer with high affinity to CRP using a CRP-immobilized Sepharose column and pre-elution procedure. Pre-elution is a method that removes the weak binding portion from a selected RNA population by washing for a short time with buffer containing CRP. By surface plasmon-resonance (SPR) analysis, the affinity constant of this aptamer for CRP was calculated to be KD = 2.25×10-9 (M). The secondary structure, contact sites with CRP protein, and application of this aptamer will be described.
Development of a DNA Aptamer for Screening Neisseria meningitidis Serogroup B by Cell SELEX
Mirzakhani, Kimia; Gargari, Seyed Latif Mousavi; Rasooli, Iraj; Rasoulinejad, Samaneh
2018-01-01
Background: Artificial oligonucleotides like DNA or RNA aptamers can be used as biodiagnostic alternatives for antibodies to detect pathogens. Comparing to antibodies, artificial oligonucleotides are produced easily at lower costs and are more stable. Neisseria meningitidis, the causative agent of meningitis, is responsible for about 1% of infections in an epidemic period. Specific DNA aptamers that bind to N. meningitidis serogroup B were identified by whole-cell Systemic Evolution of Ligands by EXponential Enrichment (SELEX). Methods: The SELEX begins with a library of labeled ssDNA molecules. After six rounds of selection and two rounds of counter-selection, 60 clones were obtained, of which the binding efficiency of 21 aptamers to the aforementioned bacterium was tested by flow cytometry. Results: The aptamers K3 and K4 showed the highest affinity to N. meningitidis serogroup B and no affinity to N. meningitidis serogroups Y, A, and C, or to other meningitis causing bacteria. The dissociation constant (Kd value) for K3 and K4 were calculated as 28.3 ± 8.9 pM and 39.1 ± 8.6 pM, respectively. K3 aptamer with the lowest Kd was chosen as the main aptamer. K3 could detect N. meningitidis in patients’ cerebrospinal fluid (CSF) samples and in CSF from healthy volunteers inoculated with N. meningitidis serogroup B (ATCC 13090) at 200 and 100 CFU ml-1, respectively. Conclusion: The findings suggest the application of the developed aptamer in specific detection of N. meningitidis serogroup B amongst a group of meningitis causing bacteria.
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.
Sypabekova, Marzhan; Bekmurzayeva, Aliya; Wang, Ronghui; Li, Yanbin; Nogues, Claude; Kanayeva, Damira
2017-05-01
Rapid detection of Mycobacterium tuberculosis (Mtb), an etiological agent of tuberculosis (TB), is important for global control of this disease. Aptamers have emerged as a potential rival for antibodies in therapeutics, diagnostics and biosensing due to their inherent characteristics. The aim of the current study was to select and characterize single-stranded DNA aptamers against MPT64 protein, one of the predominant secreted proteins of Mtb pathogen. Aptamers specific to MPT64 protein were selected in vitro using systematic evolution of ligands through exponential enrichment (SELEX) method. The selection was started with a pool of ssDNA library with randomized 40-nucleotide region. A total of 10 cycles were performed and seventeen aptamers with unique sequences were identified by sequencing. Dot Blot analysis was performed to monitor the SELEX process and to conduct the preliminary tests on the affinity and specificity of aptamers. Enzyme linked oligonucleotide assay (ELONA) showed that most of the aptamers were specific to the MPT64 protein with a linear correlation of R 2 = 0.94 for the most selective. Using Surface Plasmon Resonance (SPR), dissociation equilibrium constant K D of 8.92 nM was obtained. Bioinformatics analysis of the most specific aptamers revealed the existence of a conserved as well as distinct sequences and possible binding site on MPT64. The specificity was determined by testing non-target ESAT-6 and CFP-10. Negligible cross-reactivity confirmed the high specificity of the selected aptamer. The selected aptamer was further tested on clinical sputum samples using ELONA and had sensitivity and specificity of 91.3% and 90%, respectively. Microscopy, culture positivity and nucleotide amplification methods were used as reference standards. The aptamers studied could be further used for the development of medical diagnostic tools and detection assays for Mtb. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Glutamate Receptor Aptamers and ALS
2008-01-01
XXGATC ACC Consensus sequence RNA library Cloning and sequencing SELEX DIAGRAM Fig. 1. (a) Flow chart of SELEX. The library we used for SELEX...recording electrode and placed ~100 µm away from the hole. The linear flow rate of the solution is 1-4 cm/s. An optical fiber through which laser light for...channel recording (26) GluR6Q 1.1 × 104 4.2 × 102 Laser-pulse photolysis (67) 1.0 × 104 4.4 × 102 Fitting (52) 1.0 × 104 Flow measurement (46
NASA Astrophysics Data System (ADS)
Birch, Christina M.; Hou, Han Wei; Han, Jongyoon; Niles, Jacquin C.
2015-07-01
Plasmodium falciparum malaria parasites invade and remodel human red blood cells (RBCs) by trafficking parasite-synthesized proteins to the RBC surface. While these proteins mediate interactions with host cells that contribute to disease pathogenesis, the infected RBC surface proteome remains poorly characterized. Here we use a novel strategy (I-SELEX) to discover high affinity aptamers that selectively recognize distinct epitopes uniquely present on parasite-infected RBCs. Based on inertial focusing in spiral microfluidic channels, I-SELEX enables stringent partitioning of cells (efficiency ≥ 106) from unbound oligonucleotides at high volume throughput (~2 × 106 cells min-1). Using an RBC model displaying a single, non-native antigen and live malaria parasite-infected RBCs as targets, we establish suitability of this strategy for de novo aptamer selections. We demonstrate recovery of a diverse set of aptamers that recognize distinct, surface-displayed epitopes on parasite-infected RBCs with nanomolar affinity, including an aptamer against the protein responsible for placental sequestration, var2CSA. These findings validate I-SELEX as a broadly applicable aptamer discovery platform that enables identification of new reagents for mapping the parasite-infected RBC surface proteome at higher molecular resolution to potentially contribute to malaria diagnostics, therapeutics and vaccine efforts.
Nucleic acid aptamers as stabilizers of proteins: the stability of tetanus toxoid.
Jain, Nishant Kumar; Jetani, Hardik C; Roy, Ipsita
2013-07-01
Exposure of tetanus toxoid to moisture leads to its aggregation and reduction of potency. The aim of this work was to use SELEX (systematic evolution of ligands by exponential enrichment) protocol and select aptamers which recognize tetanus toxoid (Mr ~150 kDa) with high affinity. Colyophilized preparations of tetanus toxoid and specific aptamers were encapsulated in PLGA microspheres and sustained release of the antigen was observed up to 55 days using different techniques. The total protein released was between 40-55% (24-45% residual antigenicity) in the presence of the aptamers as compared to 25% (11% residual antigenicity) for the antigen alone. We show that instead of inhibiting absorption of moisture, the aptamers blocked the protein unfolding upon absorption of moisture, inhibiting the initiation of aggregation. When exposed to accelerated storage conditions, some of the RNA sequences were able to inhibit moisture-induced aggregation in vitro and retain antigenicity of tetanus toxoid. Nucleic acid aptamers represent a novel class of protein stabilizers which stabilize the protein by interacting directly with it. This mechanism is unlike that of small molecules which alter the medium properties and hence depend on the stress condition a protein is exposed to.
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.
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.
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.
Modulation of RNA function by aminoglycoside antibiotics.
Schroeder, R; Waldsich, C; Wank, H
2000-01-04
One of the most important families of antibiotics are the aminoglycosides, including drugs such as neomycin B, paromomycin, gentamicin and streptomycin. With the discovery of the catalytic potential of RNA, these antibiotics became very popular due to their RNA-binding capacity. They serve for the analysis of RNA function as well as for the study of RNA as a potential therapeutic target. Improvements in RNA structure determination recently provided first insights into the decoding site of the ribosome at high resolution and how aminoglycosides might induce misreading of the genetic code. In addition to inhibiting prokaryotic translation, aminoglycosides inhibit several catalytic RNAs such as self-splicing group I introns, RNase P and small ribozymes in vitro. Furthermore, these antibiotics interfere with human immunodeficiency virus (HIV) replication by disrupting essential RNA-protein contacts. Most exciting is the potential of many RNA-binding antibiotics to stimulate RNA activities, conceiving small-molecule partners for the hypothesis of an ancient RNA world. SELEX (systematic evolution of ligands by exponential enrichment) has been used in this evolutionary game leading to small synthetic RNAs, whose NMR structures gave valuable information on how aminoglycosides interact with RNA, which could possibly be used in applied science.
Bogani, Debora; Morgan, Marc A. J.; Nelson, Andrew C.; Costello, Ita; McGouran, Joanna F.; Kessler, Benedikt M.
2013-01-01
Prdm4 is a highly conserved member of the Prdm family of PR/SET domain zinc finger proteins. Many well-studied Prdm family members play critical roles in development and display striking loss-of-function phenotypes. Prdm4 functional contributions have yet to be characterized. Here, we describe its widespread expression in the early embryo and adult tissues. We demonstrate that DNA binding is exclusively mediated by the Prdm4 zinc finger domain, and we characterize its tripartite consensus sequence via SELEX (systematic evolution of ligands by exponential enrichment) and ChIP-seq (chromatin immunoprecipitation-sequencing) experiments. In embryonic stem cells (ESCs), Prdm4 regulates key pluripotency and differentiation pathways. Two independent strategies, namely, targeted deletion of the zinc finger domain and generation of a EUCOMM LacZ reporter allele, resulted in functional null alleles. However, homozygous mutant embryos develop normally and adults are healthy and fertile. Collectively, these results strongly suggest that Prdm4 functions redundantly with other transcriptional partners to cooperatively regulate gene expression in the embryo and adult animal. PMID:23918801
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.
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.
Advances in the Study of Aptamer-Protein Target Identification Using the Chromatographic Approach.
Drabik, Anna; Ner-Kluza, Joanna; Mielczarek, Przemyslaw; Civit, Laia; Mayer, Günter; Silberring, Jerzy
2018-06-01
Ever since the development of the process known as the systematic evolution of ligands by exponential enrichment (SELEX), aptamers have been widely used in a variety of studies, including the exploration of new diagnostic tools and the discovery of new treatment methods. Aptamers' ability to bind to proteins with high affinity and specificity, often compared to that of antibodies, enables the search for potential cancer biomarkers and helps us understand the mechanisms of carcinogenesis. The blind spot of those investigations is usually the difficulty in the selective extraction of targets attached to the aptamer. There are many studies describing the cell SELEX for the prime choice of aptamers toward living cancer cells or even whole tumors in the animal models. However, a dilemma arises when a large number of proteins are being identified as potential targets, which is often the case. In this article, we present a new analytical approach designed to selectively target proteins bound to aptamers. During studies, we have focused on the unambiguous identification of the molecular targets of aptamers characterized by high specificity to the prostate cancer cells. We have compared four assay approaches using electrophoretic and chromatographic methods for "fishing out" aptamer protein targets followed by mass spectrometry identification. We have established a new methodology, based on the fluorescent-tagged oligonucleotides commonly used for flow-cytometry experiments or as optic aptasensors, that allowed the detection of specific aptamer-protein interactions by mass spectrometry. The use of atto488-labeled aptamers for the tracking of the formation of specific aptamer-target complexes provides the possibility of studying putative protein counterparts without needing to apply enrichment techniques. Significantly, changes in the hydrophobic properties of atto488-labeled aptamer-protein complexes facilitate their separation by reverse-phase chromatography combined with fluorescence detection followed by mass-spectrometry-based protein identification. These comparative results of several methodological approaches confirmed the universal applicability of this method to studying aptamer-protein interactions with high sensitivity, showing superior properties compared with pull-down techniques.
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.
Bayne, Charlie F; Widawski, Max E; Gao, Feng; Masab, Mohammed H; Chattopadhyay, Maitreyi; Murawski, Allison M; Sansevere, Robert M; Lerner, Bryan D; Castillo, Rinaldys J; Griesman, Trevor; Fu, Jiantao; Hibben, Jennifer K; Garcia-Perez, Alma D; Simon, Anne E; Kushner, David B
2018-07-01
Noncoding RNAs use their sequence and/or structure to mediate function(s). The 5' portion (166 nt) of the 356-nt noncoding satellite RNA C (satC) of Turnip crinkle virus (TCV) was previously modeled to contain a central region with two stem-loops (H6 and H7) and a large connecting hairpin (H2). We now report that in vivo functional selection (SELEX) experiments assessing sequence/structure requirements in H2, H6, and H7 reveal that H6 loop sequence motifs were recovered at nonrandom rates and only some residues are proposed to base-pair with accessible complementary sequences within the 5' central region. In vitro SHAPE of SELEX winners indicates that the central region is heavily base-paired, such that along with the lower stem and H2 region, one extensive hairpin exists composing the entire 5' region. As these SELEX winners are highly fit, these characteristics facilitate satRNA amplification in association with TCV in plants. Copyright © 2018 Elsevier Inc. All rights reserved.
Aptamers and the RNA World, Past and Present
Gold, Larry; Janjic, Nebojsa; Jarvis, Thale; Schneider, Dan; Walker, Jeffrey J.; Wilcox, Sheri K.; Zichi, Dom
2012-01-01
Summary Aptamers and the SELEX process were discovered over two decades ago. These discoveries have spawned a productive academic and commercial industry. The collective results provide insights into biology, past and present, through an in vitro evolutionary exploration of the nature of nucleic acids and their potential roles in ancient life. Aptamers have helped usher in an RNA renaissance. Here we explore some of the evolution of the aptamer field and the insights it has provided for conceptualizing an RNA world, from its nascence to our current endeavor employing aptamers in human proteomics to discover biomarkers of health and disease. PMID:21441582
Layzer, Juliana M; Sullenger, Bruce A
2007-01-01
By using the in vitro selection method SELEX against the complex mixture of GLA proteins and utilizing methods to deconvolute the resulting ligands, we were able to successfully generate 2'-ribo purine, 2'-fluoro pyrimidine aptamers to various individual targets in the GLA protein proteome that ranged in concentration from 10 nM to 1.4 microM in plasma. Perhaps not unexpectedly, the majority of the aptamers isolated following SELEX bind the most abundant protein in the mixture, prothrombin (FII), with high affinity. We show that by deselecting the dominant prothrombin aptamer the selection can be redirected. By using this DeSELEX approach, we were able to shift the selection toward other sequences and to less abundant protein targets and obtained an aptamer to Factor IX (FIX). We also demonstrate that by using an RNA library that is focused around a proteome, purified protein targets can then be used to rapidly generate aptamers to the protein targets that are rare in the initial mixture such as Factor VII (FVII) and Factor X (FX). Moreover, for all four proteins targeted (FII, FVII, FIX, and FX), aptamers were identified that could inhibit the individual protein's activitity in coagulation assays. Thus, by applying the concepts of DeSELEX and focused library selection, aptamers specific for any protein in a particular proteome can theoretically be generated, even when the proteins in the mixture are present at very different concentrations.
NASA Astrophysics Data System (ADS)
Tsao, Shih-Ming; Lai, Ji-Ching; Horng, Horng-Er; Liu, Tu-Chen; Hong, Chin-Yih
2017-04-01
Aptamers are oligonucleotides that can bind to specific target molecules. Most aptamers are generated using random libraries in the standard systematic evolution of ligands by exponential enrichment (SELEX). Each random library contains oligonucleotides with a randomized central region and two fixed primer regions at both ends. The fixed primer regions are necessary for amplifying target-bound sequences by PCR. However, these extra-sequences may cause non-specific bindings, which potentially interfere with good binding for random sequences. The Magnetic-Assisted Rapid Aptamer Selection (MARAS) is a newly developed protocol for generating single-strand DNA aptamers. No repeat selection cycle is required in the protocol. This study proposes and demonstrates a method to isolate aptamers for C-reactive proteins (CRP) from a randomized ssDNA library containing no fixed sequences at 5‧ and 3‧ termini using the MARAS platform. Furthermore, the isolated primer-free aptamer was sequenced and binding affinity for CRP was analyzed. The specificity of the obtained aptamer was validated using blind serum samples. The result was consistent with monoclonal antibody-based nephelometry analysis, which indicated that a primer-free aptamer has high specificity toward targets. MARAS is a feasible platform for efficiently generating primer-free aptamers for clinical diagnoses.
Stewart, H.; Bingham, R.J.; White, S. J.; Dykeman, E. C.; Zothner, C.; Tuplin, A. K.; Stockley, P. G.; Twarock, R.; Harris, M.
2016-01-01
The specific packaging of the hepatitis C virus (HCV) genome is hypothesised to be driven by Core-RNA interactions. To identify the regions of the viral genome involved in this process, we used SELEX (systematic evolution of ligands by exponential enrichment) to identify RNA aptamers which bind specifically to Core in vitro. Comparison of these aptamers to multiple HCV genomes revealed the presence of a conserved terminal loop motif within short RNA stem-loop structures. We postulated that interactions of these motifs, as well as sub-motifs which were present in HCV genomes at statistically significant levels, with the Core protein may drive virion assembly. We mutated 8 of these predicted motifs within the HCV infectious molecular clone JFH-1, thereby producing a range of mutant viruses predicted to possess altered RNA secondary structures. RNA replication and viral titre were unaltered in viruses possessing only one mutated structure. However, infectivity titres were decreased in viruses possessing a higher number of mutated regions. This work thus identified multiple novel RNA motifs which appear to contribute to genome packaging. We suggest that these structures act as cooperative packaging signals to drive specific RNA encapsidation during HCV assembly. PMID:26972799
Dorraj, Ghamar Soltan; Rassaee, Mohammad Javad; Latifi, Ali Mohammad; Pishgoo, Bahram; Tavallaei, Mahmood
2015-08-20
Troponin T and I are ideal markers which are highly sensitive and specific for myocardial injury and have shown better efficacy than earlier markers. Since aptamers are ssDNA or RNA that bind to a wide variety of target molecules, the purpose of this research was to select an aptamer from a 79bp single-stranded DNA (ssDNA) random library that was used to bind the Human Cardiac Troponin I from a synthetic nucleic acids library by systematic evolution of ligands exponential enrichment (Selex) based on several selection and amplification steps. Human Cardiac Troponin I protein was coated onto the surface of streptavidin magnetic beads to extract specific aptamer from a large and diverse random ssDNA initial oligonucleotide library. As a result, several aptamers were selected and further examined for binding affinity and specificity. Finally TnIApt 23 showed beast affinity in nanomolar range (2.69nM) toward the target protein. A simple and rapid colorimetric detection assay for Human Cardiac Troponin I using the novel and specific aptamer-AuNPs conjugates based on dot blot assay was developed. The detection limit for this protein using aptamer-AuNPs-based assay was found to be 5ng/ml. Copyright © 2015 Elsevier B.V. All rights reserved.
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.
Fenstermacher, Katherine J; Achuthan, Vasudevan; Schneider, Thomas D; DeStefano, Jeffrey J
2018-01-16
DNA polymerases (DNAPs) recognize 3' recessed termini on duplex DNA and carry out nucleotide catalysis. Unlike promoter-specific RNA polymerases (RNAPs), no sequence specificity is required for binding or initiation of catalysis. Despite this, previous results indicate that viral reverse transcriptases bind much more tightly to DNA primers that mimic the polypurine tract. In the current report, primer sequences that bind with high affinity to Taq and Klenow polymerases were identified using a modified Selective Evolution of Ligands by Exponential Enrichment (SELEX) approach. Two Taq -specific primers that bound ∼10 (Taq1) and over 100 (Taq2) times more stably than controls to Taq were identified. Taq1 contained 8 nucleotides (5' -CACTAAAG-3') that matched the phage T3 RNAP "core" promoter. Both primers dramatically outcompeted primers with similar binding thermodynamics in PCR reactions. Similarly, exonuclease minus Klenow polymerase also selected a high affinity primer that contained a related core promoter sequence from phage T7 RNAP (5' -ACTATAG-3'). For both Taq and Klenow, even small modifications to the sequence resulted in large losses in binding affinity suggesting that binding was highly sequence-specific. The results are discussed in the context of possible effects on multi-primer (multiplex) PCR assays, molecular information theory, and the evolution of RNAPs and DNAPs. Importance This work further demonstrates that primer-dependent DNA polymerases can have strong sequence biases leading to dramatically tighter binding to specific sequences. These may be related to biological function, or be a consequences of the structural architecture of the enzyme. New sequence specificity for Taq and Klenow polymerases were uncovered and among them were sequences that contained the core promoter elements from T3 and T7 phage RNA polymerase promoters. This suggests the intriguing possibility that phage RNA polymerases exploited intrinsic binding affinities of ancestral DNA polymerases to develop their promotors. Conversely, DNA polymerases could have evolved from related RNA polymerases and retained the intrinsic binding preference despite there being no clear function for such a preference in DNA biology. Copyright © 2018 American Society for Microbiology.
Molecular Elucidation of Disease Biomarkers at the Interface of Chemistry and Biology.
Zhang, Liqin; Wan, Shuo; Jiang, Ying; Wang, Yanyue; Fu, Ting; Liu, Qiaoling; Cao, Zhijuan; Qiu, Liping; Tan, Weihong
2017-02-22
Disease-related biomarkers are objectively measurable molecular signatures of physiological status that can serve as disease indicators or drug targets in clinical diagnosis and therapy, thus acting as a tool in support of personalized medicine. For example, the prostate-specific antigen (PSA) biomarker is now widely used to screen patients for prostate cancer. However, few such biomarkers are currently available, and the process of biomarker identification and validation is prolonged and complicated by inefficient methods of discovery and few reliable analytical platforms. Therefore, in this Perspective, we look at the advanced chemistry of aptamer molecules and their significant role as molecular probes in biomarker studies. As a special class of functional nucleic acids evolved from an iterative technology termed Systematic Evolution of Ligands by Exponential Enrichment (SELEX), these single-stranded oligonucleotides can recognize their respective targets with selectivity and affinity comparable to those of protein antibodies. Because of their fast turnaround time and exceptional chemical properties, aptamer probes can serve as novel molecular tools for biomarker investigations, particularly in assisting identification of new disease-related biomarkers. More importantly, aptamers are able to recognize biomarkers from complex biological environments such as blood serum and cell surfaces, which can provide direct evidence for further clinical applications. This Perspective highlights several major advancements of aptamer-based biomarker discovery strategies and their potential contribution to the practice of precision medicine.
Transcription factor DecR (YbaO) controls detoxification of L-cysteine in Escherichia coli.
Shimada, Tomohiro; Tanaka, Kan; Ishihama, Akira
2016-09-01
YbaO is an uncharacterized AsnC-family transcription factor of Escherichia coli. In both Salmonella enterica and Pantoea ananatis, YbaO homologues were identified to regulate the adjacent gene encoding cysteine desulfhydrase for detoxification of cysteine. Using the genomic SELEX (systematic evolution of ligands by exponential enrichment) screening system, we identified the yhaOM operon, located far from the ybaO gene on the E. coli genome, as a single regulatory target of YbaO. In both gel shift assay in vitro and reporter and Northern blot assays in vivo, YbaO was found to regulate the yhaOM promoter. The growth of mutants lacking either ybaO or its targets yhaOM was delayed in the presence of cysteine, indicating involvement of these genes in cysteine detoxification. In the major pathway of cysteine degradation, hydrogen sulfide is produced in wild-type E. coli, but its production was not observed in each of the ybaO, yhaO and yhaM mutants. The yhaOM promoter was activated in the presence of cysteine, implying the role of cysteine in activation of YbaO. Taken together, we propose that YbaO is the cysteine-sensing transcriptional activator of the yhaOM operon, which is involved in the detoxification of cysteine. We then propose the naming of ybaO as decR (regulator of detoxification of cysteine).
In vitro isolation of small-molecule-binding aptamers with intrinsic dye-displacement functionality
Yu, Haixiang; Yang, Weijuan; Alkhamis, Obtin; Canoura, Juan; Yang, Kyung-Ae; Xiao, Yi
2018-01-01
Abstract Aptamer-based sensors offer a powerful tool for molecular detection, but the practical implementation of these biosensors is hindered by costly and laborious sequence engineering and chemical modification procedures. We report a simple strategy for directly isolating signal-reporting aptamers in vitro through systematic evolution of ligands by exponential enrichment (SELEX) that transduce binding events into a detectable change of absorbance via target-induced displacement of a small-molecule dye. We first demonstrate that diethylthiatricarbocyanine (Cy7) can stack into DNA three-way junctions (TWJs) in a sequence-independent fashion, greatly altering the dye's absorbance spectrum. We then design a TWJ-containing structured library and isolate an aptamer against 3,4-methylenedioxypyrovalerone (MDPV), a synthetic cathinone that is an emerging drug of abuse. This aptamer intrinsically binds Cy7 within its TWJ domain, but MDPV efficiently displaces the dye, resulting in a change in absorbance within seconds. This assay is label-free, and detects nanomolar concentrations of MDPV. It also recognizes other synthetic cathinones, offering the potential to detect newly-emerging designer drugs, but does not detect structurally-similar non-cathinone compounds or common cutting agents. Moreover, we demonstrate that the Cy7-displacement colorimetric assay is more sensitive than a conventional strand-displacement fluorescence assay. We believe our strategy offers an effective generalized approach for the development of sensitive dye-displacement colorimetric assays for other small-molecule targets. PMID:29361056
Wang, Deng-Liang; Song, Yan-Ling; Zhu, Zhi; Li, Xi-Lan; Zou, Yuan; Yang, Hai-Tao; Wang, Jiang-Jie; Yao, Pei-Sen; Pan, Ru-Jun; Yang, Chaoyong James; Kang, De-Zhi
2014-10-31
Epidermal growth factor receptor (EGFR/HER1/c-ErbB1), is overexpressed in many solid cancers, such as epidermoid carcinomas, malignant gliomas, etc. EGFR plays roles in proliferation, invasion, angiogenesis and metastasis of malignant cancer cells and is the ideal antigen for clinical applications in cancer detection, imaging and therapy. Aptamers, the output of the systematic evolution of ligands by exponential enrichment (SELEX), are DNA/RNA oligonucleotides which can bind protein and other substances with specificity. RNA aptamers are undesirable due to their instability and high cost of production. Conversely, DNA aptamers have aroused researcher's attention because they are easily synthesized, stable, selective, have high binding affinity and are cost-effective to produce. In this study, we have successfully identified DNA aptamers with high binding affinity and selectivity to EGFR. The aptamer named TuTu22 with Kd 56±7.3nM was chosen from the identified DNA aptamers for further study. Flow cytometry analysis results indicated that the TuTu22 aptamer was able to specifically recognize a variety of cancer cells expressing EGFR but did not bind to the EGFR-negative cells. With all of the aforementioned advantages, the DNA aptamers reported here against cancer biomarker EGFR will facilitate the development of novel targeted cancer detection, imaging and therapy. Copyright © 2014 Elsevier Inc. All rights reserved.
Tuma Sabah, Jinan; Zulkifli, Razauden Mohamed; Shahir, Shafinaz; Ahmed, Farediah; Abdul Kadir, Mohammed Rafiq; Zakaria, Zarita
2018-05-15
Distinctive bioactivities possessed by luteolin (3', 4', 5, 7-tetrahydroxy-flavone) are advantageous for sundry practical applications. This paper reports the in vitro selection and characterization of single stranded-DNA (ssDNA) aptamers, specific for luteolin (LUT). 76-mer library containing 1015 randomized ssDNA were screened via systematic evolution of ligands by exponential enrichment (SELEX). The recovered ssDNA pool from the 8th round was amplified with unlabeled primers and cloned into PSTBlue-1 vector prior to sequencing. 22 of LUT-binding aptamer variants were further classified into one of the seven groups based on their N40 random sequence regions, wherein one representative from each group was characterized. The dissociation constant of aptamers designated as LUT#28, LUT#20 and LUT#3 was discerned to be 107, 214 and 109 nM, respectively with high binding affinity towards LUT. Prediction analysis of the secondary structure suggested discrete features with typical loop and stem motifs. Furthermore, LUT#3 displayed higher specificity with insignificant binding toward kaempferol and quercetin despite its structural and functional similarity compared to LUT#28 and LUT#20. Further LUT#3 can detect free luteolin within 0.2-1 mM in solution. It was suggested that LUT#3 aptamer were the most suitable for LUT recognition tool at laboratory scale based on the condition tested. Copyright © 2018 Elsevier Inc. All rights reserved.
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
Evolution and Protein Packaging of Small Molecule RNA Aptamers
Lau, Jolene L.; Baksh, Michael M.; Fiedler, Jason D.; Brown, Steven D.; Kussrow, Amanda; Bornhop, Darryl J.; Ordoukhanian, Phillip
2011-01-01
A high-affinity RNA aptamer (Kd = 50 nM) was efficiently identified by SELEX against a heteroaryl dihydropyrimidine structure, chosen as a representative drug-like molecule with no cross reactivity with mammalian or bacterial cells. This aptamer, its weaker-binding variants, and a known aptamer against theophylline were each embedded in a longer RNA sequence that was encapsidated inside a virus-like particle by a convenient expression technique. These nucleoprotein particles were shown by backscattering interferometry to bind to the small-molecule ligands with affinities similar to those of the free (non-encapsidated) aptamers. The system therefore comprises a general approach to the production and sequestration of functional RNA molecules, characterized by a convenient label-free analytical technique. PMID:21899290
Selection and Characterization of Single Stranded DNA Aptamers for the Hormone Abscisic Acid
Gonzalez, Victor M.; Millo, Enrico; Sturla, Laura; Vigliarolo, Tiziana; Bagnasco, Luca; Guida, Lucrezia; D'Arrigo, Cristina; De Flora, Antonio; Salis, Annalisa; Martin, Elena M.; Bellotti, Marta; Zocchi, Elena
2013-01-01
The hormone abscisic acid (ABA) is a small molecule involved in pivotal physiological functions in higher plants. Recently, ABA has been also identified as an endogenous hormone in mammals, regulating different cell functions including inflammatory processes, stem cell expansion, insulin release, and glucose uptake. Aptamers are short, single-stranded (ss) oligonucleotidesable to recognize target molecules with high affinity. The small size of the ABA molecule represented a challenge for aptamer development and the aim of this study was to develop specific anti-ABA DNA aptamers. Biotinylated abscisic acid (bio-ABA) was immobilized on streptavidin-coated magnetic beads. DNA aptamers against bio-ABA were selected with 7 iterative rounds of the systematic evolution of ligands by exponential enrichment method (SELEX), each round comprising incubation of the ABA-binding beads with the ssDNA sequences, DNA elution, electrophoresis, and polymerase chain reaction (PCR) amplification. The PCR product was cloned and sequenced. The binding affinity of several clones was determined using bio-ABA immobilized on streptavidin-coated plates. Aptamer 2 and aptamer 9 showed the highest binding affinity, with dissociation constants values of 0.98±0.14 μM and 0.80±0.07 μM, respectively. Aptamers 2 and 9 were also able to bind free, unmodified ABA and to discriminate between different ABA enantiomers and isomers. Our findings indicate that ssDNA aptamers can selectively bind ABA and could be used for the development of ABA quantitation assays. PMID:23971905
Wu, Shijia; Duan, Nuo; Shi, Zhao; Fang, Congcong; Wang, Zhouping
2014-03-18
A highly sensitive and specific multiplex method for the simultaneous detection of three pathogenic bacteria was fabricated using multicolor upconversion nanoparticles (UCNPs) as luminescence labels coupled with aptamers as the molecular recognition elements. Multicolor UCNPs were synthesized via doping with various rare-earth ions to obtain well-separated emission peaks. The aptamer sequences were selected using the systematic evolution of ligands by exponential enrichment (SELEX) strategy for Staphylococcus aureus, Vibrio parahemolyticus, and Salmonella typhimurium. When applied in this method, aptamers can be used for the specific recognition of the bacteria from complex mixtures, including those found in real food matrixes. Aptamers and multicolor UCNPs were employed to selectively capture and simultaneously quantify the three target bacteria on the basis of the independent peaks. Under optimal conditions, the correlation between the concentration of three bacteria and the luminescence signal was found to be linear from 50-10(6) cfu mL(-1). Improved by the magnetic separation and concentration effect of Fe3O4 magnetic nanoparticles, the limits of detection of the developed method were found to be 25, 10, and 15 cfu mL(-1) for S. aureus, V. parahemolyticus, and S. typhimurium, respectively. The capability of the bioassay in real food samples was also investigated, and the results were consistent with experimental results obtained from plate-counting methods. This proposed method for the detection of various pathogenic bacteria based on multicolor UCNPs has great potential in the application of food safety and multiplex nanosensors.
Hu, Lujun; Wang, Linlin; Lu, Wenwei; Zhao, Jianxin; Zhang, Hao; Chen, Wei
2017-01-01
A whole-bacterium-based SELEX (Systematic Evolution of Ligands by Exponential Enrichment) procedure was adopted in this study for the selection of an ssDNA aptamer that binds to Bifidobacterium bifidum. After 12 rounds of selection targeted against B. bifidum, 30 sequences were obtained and divided into seven families according to primary sequence homology and similarity of secondary structure. Four FAM (fluorescein amidite) labeled aptamer sequences from different families were selected for further characterization by flow cytometric analysis. The results reveal that the aptamer sequence CCFM641-5 demonstrated high-affinity and specificity for B. bifidum compared with the other sequences tested, and the estimated Kd value was 10.69 ± 0.89 nM. Additionally, sequence truncation experiments of the aptamer CCFM641-5 led to the conclusion that the 5′-primer and 3′-primer binding sites were essential for aptamer-target binding. In addition, the possible component of the target B. bifidum, bound by the aptamer CCFM641-5, was identified as a membrane protein by treatment with proteinase. Furthermore, to prove the potential application of the aptamer CCFM641-5, a colorimetric bioassay of the sandwich-type structure was used to detect B. bifidum. The assay had a linear range of 104 to 107 cfu/mL (R2 = 0.9834). Therefore, the colorimetric bioassay appears to be a promising method for the detection of B. bifidum based on the aptamer CCFM641-5. PMID:28441340
DNA aptamers as a novel approach to neutralize Staphylococcus aureus α-toxin.
Vivekananda, Jeevalatha; Salgado, Christi; Millenbaugh, Nancy J
2014-02-14
Staphylococcus aureus is a versatile pathogen capable of causing a broad spectrum of diseases ranging from superficial skin infections to life threatening conditions such as endocarditis, septicemia, pneumonia and toxic shock syndrome. In vitro and in vivo studies identified an exotoxin, α-toxin, as a major cause of S. aureus toxicity. Because S. aureus has rapidly evolved resistance to a number of antibiotics, including methicillin, it is important to identify new therapeutic strategies, other than antibiotics, for inhibiting the harmful effects of this pathogen. Aptamers are single-stranded DNA or RNA oligonucleotides with three-dimensional folded conformations that bind with high affinity and selectivity to targets and modulate their biological functions. The goal of this study was to isolate DNA aptamers that specifically inhibit the cytotoxic activity of α-toxin. After 10 rounds of Systematic Evolution of Ligands by EXponential Enrichment (SELEX), 49 potential anti-α-toxin aptamers were identified. In vitro neutralization assays demonstrated that 4 of these 49 aptamers, AT-27, AT-33, AT-36, and AT-49, significantly inhibited α-toxin-mediated cell death in Jurkat T cells. Furthermore, RT-PCR analysis revealed that α-toxin increased the transcription of the inflammatory cytokines TNF-α and IL-17 and that anti-α-toxin aptamers AT-33 and AT-36 inhibited the upregulation of these genes. Collectively, the data suggest the feasibility of generating functionally effective aptamers against α-toxin for treatment of S. aureus infections. Published by Elsevier Inc.
Viola, Ivana L; Uberti Manassero, Nora G; Ripoll, Rodrigo; Gonzalez, Daniel H
2011-04-01
The TCP domain is a DNA-binding domain present in plant transcription factors that modulate different processes. In the present study, we show that Arabidopsis class I TCP proteins are able to interact with a dyad-symmetric sequence composed of two GTGGG half-sites. TCP20 establishes symmetric interactions with the 5' half of each strand, whereas TCP11 interacts mainly with the 3' half. SELEX (systematic evolution of ligands by exponential enrichment) experiments with TCP15 and TCP20 indicated that these proteins have similar, although not identical, DNA-binding preferences and are able to interact with non-palindromic binding sites of the type GTGGGNCCNN. TCP11 shows a different DNA-binding specificity, with a preference for the sequence GTGGGCCNNN. The distinct DNA-binding properties of TCP11 are due to the presence of a threonine residue at position 15 of the TCP domain, a position that is occupied by an arginine residue in most TCP proteins. TCP11 also forms heterodimers with TCP15 that have increased DNA-binding efficiency. The expression in plants of a repressor form of TCP11 demonstrated that this protein is a developmental regulator that influences the growth of leaves, stems and petioles, and pollen development. The results suggest that changes in DNA-binding preferences may be one of the mechanisms through which class I TCP proteins achieve functional specificity.
Development of structure switching aptamer assay for detection of aflatoxin M1 in milk sample.
Sharma, Atul; Catanante, Gaëlle; Hayat, Akhtar; Istamboulie, Georges; Ben Rejeb, Ines; Bhand, Sunil; Marty, Jean Louis
2016-09-01
The discovery of in-vitro systematic evolution of ligands by exponential enrichment (SELEX) process has considerably broaden the utility of aptamer as bio-recognition element, providing the high binding affinity and specificity against the target analytes. Recent research has focused on the development of structure switching signaling aptamer assay, transducing the aptamer- target recognition event into an easily detectable signal. In this paper, we demonstrate the development of structure switching aptamer assay for determination of aflatoxin M1 (AFM1) employing the quenching-dequenching mechanism. Hybridization of fluorescein labelled anti-AFM1 aptamer (F-aptamer) with TAMRA labelled complementary sequences (Q-aptamer) brings the fluorophore and the quencher into close proximity, which results in maximum fluorescence quenching. On addition of AFM1, the target induced conformational formation of antiparallel G-quadruplex aptamer-AFM1 complex results in fluorescence recovery. Under optimized experimental conditions, the developed method showed the good linearity with limit of detection (LOD) at 5.0ngkg(-1) for AFM1. The specificity of the sensing platform was carefully investigated against aflatoxin B1 (AFB1) and ochratoxin A (OTA). The developed assay platform showed the high specificity towards AFM1. The practical application of the developed aptamer assay was verified for detection of AFM1 in spiked milk samples. Good recoveries were obtained in the range from 94.40% to 95.28% (n=3) from AFM1 spiked milk sample. Copyright © 2016. Published by Elsevier B.V.
Yokoyama, Katsushi; Nogami, Hideki; Kabasawa, Mamiko; Ebihara, Sonomi; Shimowasa, Ai; Hashimoto, Keiko; Kawashima, Tsuyoshi; Ishijima, Sanae A.; Suzuki, Masashi
2009-01-01
The DNA-binding mode of archaeal feast/famine-regulatory proteins (FFRPs), i.e. paralogs of the Esherichia coli leucine-responsive regulatory protein (Lrp), was studied. Using the method of systematic evolution of ligands by exponential enrichment (SELEX), optimal DNA duplexes for interacting with TvFL3, FL10, FL11 and Ss-LrpB were identified as TACGA[AAT/ATT]TCGTA, GTTCGA[AAT/ATT]TCGAAC, CCGAAA[AAT/ATT]TTTCGG and TTGCAA[AAT/ATT]TTGCAA, respectively, all fitting into the form abcdeWWWedcba. Here W is A or T, and e.g. a and a are bases complementary to each other. Apparent equilibrium binding constants of the FFRPs and various DNA duplexes were determined, thereby confirming the DNA-binding specificities of the FFRPs. It is likely that these FFRPs recognize DNA in essentially the same way, since their DNA-binding specificities were all explained by the same pattern of relationship between amino-acid positions and base positions to form chemical interactions. As predicted from this relationship, when Gly36 of TvFL3 was replaced by Thr, the b base in the optimal DNA duplex changed from A to T, and, when Thr36 of FL10 was replaced by Ser, the b base changed from T to G/A. DNA-binding characteristics of other archaeal FFRPs, Ptr1, Ptr2, Ss-Lrp and LysM, are also consistent with the relationship. PMID:19468044
Agyei, Dominic; Acquah, Caleb; Tan, Kei Xian; Hii, Hieng Kok; Rajendran, Subin R C K; Udenigwe, Chibuike C; Danquah, Michael K
2018-01-01
Food-derived bioactive proteins and peptides have gained acceptance among researchers, food manufacturers and consumers as health-enhancing functional food components that also serve as natural alternatives for disease prevention and/or management. Bioactivity in food proteins and peptides is determined by their conformations and binding characteristics, which in turn depend on their primary and secondary structures. To maintain their bioactivities, the molecular integrity of bioactive peptides must remain intact, and this warrants the study of peptide form and structure, ideally with robust, highly specific and sensitive techniques. Short single-stranded nucleic acids (i.e. aptamers) are known to have high affinity for cognate targets such as proteins and peptides. Aptamers can be produced cost-effectively and chemically derivatized to increase their stability and shelf life. Their improved binding characteristics and minimal modification of the target molecular signature suggests their suitability for real-time detection of conformational changes in both proteins and peptides. This review discusses the developmental progress of systematic evolution of ligands by exponential enrichment (SELEX), an iterative technology for generating cost-effective aptamers with low dissociation constants (K d ) for monitoring the form and structure of bioactive proteins and peptides. The review also presents case studies of this technique in monitoring the structural stability of bioactive peptide formulations to encourage applications in functional foods. The challenges and potential of aptamers in this research field are also discussed. Graphical abstract Advancing bioactive proteins and peptide functionality via aptameric ligands.
Nigmatkulov, G. A.; et al.
2015-12-18
We report the measurement of the one-dimensional charged kaon correlation functions using 600 GeV/c Σ –, π – and 540 GeV/C ρ beams from the SELEX (E781) experiment at the Fermilab Tevatron. K ±K ± correlation functions are studied for three transverse pair momentum, kT, ranges and parameterized by a Gaussian form. The emission source radii, R, and the correlation strength, λ, are extracted. Furthermore, the analysis shows a decrease of the source radii with increasing kaon transverse pair momentum for all beam types.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brodsky, Stanley
2017-01-01
In this paper we show that the intrinsic heavy-quark QCD mechanism for the hadroproduction of heavy hadrons at largemore » $$x_F$$ can resolve the apparent conflict between measurements of double-charm baryons by the SELEX fixed-target experiment and the LHCb experiment at the LHC collider. We show that both experiments are compatible, and that both results can be correct. The observed spectroscopy of double-charm hadrons is in agreement with the predictions of supersymmetric light front holographic QCD.« less
Cibiel, Agnes; Nguyen Quang, Nam; Gombert, Karine; Thézé, Benoit; Garofalakis, Anikitos; Ducongé, Frédéric
2014-01-01
Background Cell-SELEX is now widely used for the selection of aptamers against cell surface biomarkers. However, despite negative selection steps using mock cells, this method sometimes results in aptamers against undesirable targets that are expressed both on mock and targeted cells. Studying these junk aptamers might be useful for further applications than those originally envisaged. Methodology/Principal Findings Cell-SELEX was performed to identify aptamers against CHO-K1 cells expressing human Endothelin type B receptor (ETBR). CHO-K1 cells were used for negative selection of aptamers. Several aptamers were identified but no one could discriminate between both cell lines. We decided to study one of these aptamers, named ACE4, and we identified that it binds to the Annexin A2, a protein overexpressed in many cancers. Radioactive binding assays and flow cytometry demonstrated that the aptamer was able to bind several cancer cell lines from different origins, particularly the MCF-7 cells. Fluorescence microscopy revealed it could be completely internalized in cells in 2 hours. Finally, the tumor targeting of the aptamer was evaluated in vivo in nude mice xenograft with MCF-7 cells using fluorescence diffuse optical tomography (fDOT) imaging. Three hours after intravenous injection, the aptamer demonstrated a significantly higher uptake in the tumor compared to a scramble sequence. Conclusions/Significance Although aptamers could be selected during cell-SELEX against other targets than those initially intended, they represent a potential source of ligands for basic research, diagnoses and therapy. Here, studying such aptamers, we identify one with high affinity for Annexin A2 that could be a promising tool for biomedical application. PMID:24489826
A mini-library of TBA analogues containing 3'-3' and 5'-5' inversion of polarity sites.
Esposito, V; Galeone, A; Mayol, L; Randazzo, A; Virgilio, A; Virno, A
2007-01-01
Several researches have been devoted to structure-activity relationship and to post-SELEX modifications of the thrombin binding aptamer (TBA), one of the first aptamers discovered by the SELEX methodology. However, no studies on TBA dealing with the effects of introduction of inversion of polarity sites have been reported yet. In this frame, we have undertaken the synthesis and the study of a mini-library composed of several TBA analogues containing a 3'-3' or a 5'-5' inversion of polarity site at different positions into the sequence. Particularly, in this article, we present preliminary results about their structural and biological properties.
Vu, Michael M. K.; Jameson, Nora E.; Masuda, Stuart J.; Lin, Dana; Larralde-Ridaura, Rosa; Lupták, Andrej
2012-01-01
SUMMARY Aptamers are structured macromolecules in vitro evolved to bind molecular targets, whereas in nature they form the ligand-binding domains of riboswitches. Adenosine aptamers of a single structural family were isolated several times from random pools but they have not been identified in genomic sequences. We used two unbiased methods, structure-based bioinformatics and human genome-based in vitro selection, to identify aptamers that form the same adenosine-binding structure in a bacterium, and several vertebrates, including humans. Two of the human aptamers map to introns of RAB3C and FGD3 genes. The RAB3C aptamer binds ATP with dissociation constants about ten times lower than physiological ATP concentration, while the minimal FGD3 aptamer binds ATP only co-transcriptionally. PMID:23102219
Selecting Fully-Modified XNA Aptamers Using Synthetic Genetics.
Taylor, Alexander I; Holliger, Philipp
2018-06-01
This unit describes the application of "synthetic genetics," i.e., the replication of xeno nucleic acids (XNAs), artificial analogs of DNA and RNA bearing alternative backbone or sugar congeners, to the directed evolution of synthetic oligonucleotide ligands (XNA aptamers) specific for target proteins or nucleic acid motifs, using a cross-chemistry selective exponential enrichment (X-SELEX) approach. Protocols are described for synthesis of diverse-sequence XNA repertoires (typically 10 14 molecules) using DNA templates, isolation and panning for functional XNA sequences using targets immobilized on solid phase or gel shift induced by target binding in solution, and XNA reverse transcription to allow cDNA amplification or sequencing. The method may be generally applied to select fully-modified XNA aptamers specific for a wide range of target molecules. © 2018 by John Wiley & Sons, Inc. Copyright © 2018 John Wiley & Sons, Inc.
Recent advances in nanoparticle based aptasensors for food contaminants.
Sharma, Richa; Ragavan, K V; Thakur, M S; Raghavarao, K S M S
2015-12-15
Food safety and hazard analysis is a prime concern of human life, thus quality assessment of food and water is the need of the day. Recent advances in nano-biotechnology play a significant role in providing possible solutions for developing highly sensitive and affordable detection tools for food analysis. Nanomaterials based aptasensors hold great potential to overcome the drawbacks of conventional analytical techniques. Aptamers comprise a novel class of highly specific bio-recognition elements which are produced by SELEX (systematic evolution of ligands by exponential enrichment) process. They bind to target molecules by folding into 3D structures that can discriminate different chiral compounds. The flexibility in making modifications in aptamers contribute to the design of biosensors, enabling the generation of bio-recognition elements for a wide variety of target molecules. Nanomaterials such as metal nanoparticles, metal nanoclusters, metal oxide nanoparticles, metal and carbon quantum dots, graphene, carbon nanotubes and nanocomposites enable higher sensitivity by signal amplification and introduce several novel transduction principles such as enhanced chemiluminescence, fluorescence, Raman signals, electrochemical signals, enhanced catalytic activity, and super-paramagnetic properties to the biosensor. Although there are a few reviews published recently which deal with the potential of aptamers in various fields, none are devoted exclusively to the potential of aptasensors based on nanomaterials for the analysis of food contaminants. Hence, the current review discusses several transduction systems and their principles used in aptamer based nanosensors which have been developed in the past five years, the challenges faced in their designing, along with their strengths and limitations. Copyright © 2015 Elsevier B.V. All rights reserved.
The zinc fingers of YY1 bind single-stranded RNA with low sequence specificity.
Wai, Dorothy C C; Shihab, Manar; Low, Jason K K; Mackay, Joel P
2016-11-02
Classical zinc fingers (ZFs) are traditionally considered to act as sequence-specific DNA-binding domains. More recently, classical ZFs have been recognised as potential RNA-binding modules, raising the intriguing possibility that classical-ZF transcription factors are involved in post-transcriptional gene regulation via direct RNA binding. To date, however, only one classical ZF-RNA complex, that involving TFIIIA, has been structurally characterised. Yin Yang-1 (YY1) is a multi-functional transcription factor involved in many regulatory processes, and binds DNA via four classical ZFs. Recent evidence suggests that YY1 also interacts with RNA, but the molecular nature of the interaction remains unknown. In the present work, we directly assess the ability of YY1 to bind RNA using in vitro assays. Systematic Evolution of Ligands by EXponential enrichment (SELEX) was used to identify preferred RNA sequences bound by the YY1 ZFs from a randomised library over multiple rounds of selection. However, a strong motif was not consistently recovered, suggesting that the RNA sequence selectivity of these domains is modest. YY1 ZF residues involved in binding to single-stranded RNA were identified by NMR spectroscopy and found to be largely distinct from the set of residues involved in DNA binding, suggesting that interactions between YY1 and ssRNA constitute a separate mode of nucleic acid binding. Our data are consistent with recent reports that YY1 can bind to RNA in a low-specificity, yet physiologically relevant manner. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.
NASA Astrophysics Data System (ADS)
Hall, Donald
Under a current award, NASA NNX 13AC13G "EXTENDING THE ASTRONOMICAL APPLICATION OF PHOTON COUNTING HgCdTe LINEAR AVALANCHE PHOTODIODE ARRAYS TO LOW BACKGROUND SPACE OBSERVATIONS" UH has used Selex SAPHIRA 320 x 256 MOVPE L-APD HgCdTe arrays developed for Adaptive Optics (AO) wavefront (WF) sensing to investigate the potential of this technology for low background space astronomy applications. After suppressing readout integrated circuit (ROIC) glow, we have placed upper limits on gain normalized dark current of 0.01 e-/sec at up to 8 volts avalanche bias, corresponding to avalanche gain of 5, and have operated with avalanche gains of up to several hundred at higher bias. We have also demonstrated detection of individual photon events. The proposed investigation would scale the format to 1536 x 1536 at 12um (the largest achievable in a standard reticule without requiring stitching) while incorporating reference pixels required at these low dark current levels. The primary objective is to develop, produce and characterize a 1.5k x 1.5k at 12um pitch MOVPE HgCdTe L-APD array, with nearly 30 times the pixel count of the 320 x 256 SAPHIRA, optimized for low background space astronomy. This will involve: 1) Selex design of a 1.5k x 1.5k at 12um pitch ROIC optimized for low background operation, silicon wafer fabrication at the German XFab foundry in 0.35 um 3V3 process and dicing/test at Selex, 2) provision by GL Scientific of a 3-side close-buttable carrier building from the heritage of the HAWAII xRG family, 3) Selex development and fabrication of 1.5k x 1.5k at 12 um pitch MOVPE HgCdTe L-APD detector arrays optimized for low background applications, 4) hybridization, packaging into a sensor chip assembly (SCA) with initial characterization by Selex and, 5) comprehensive characterization of low background performance, both in the laboratory and at ground based telescopes, by UH. The ultimate goal is to produce and eventually market a large format array, the L-APD equivalent of the Teledyne H1RG and H2RG, able to achieve sub-electron read noise and count 1 - 5 um photons with high quantum efficiency and low dark count rate while preserving their Poisson statistics and noise.
In vivo SELEX for Identification of Brain-penetrating Aptamers
Cheng, Congsheng; Chen, Yong Hong; Lennox, Kim A; Behlke, Mark A; Davidson, Beverly L
2013-01-01
The physiological barriers of the brain impair drug delivery for treatment of many neurological disorders. One delivery approach that has not been investigated for their ability to penetrate the brain is RNA-based aptamers. These molecules can impart delivery to peripheral tissues and circulating immune cells, where they act as ligand mimics or can be modified to carry payloads. We developed a library of aptamers and an in vivo evolution protocol to determine whether specific aptamers could be identified that would home to the brain after injection into the peripheral vasculature. Unlike biopanning with recombinant bacteriophage libraries, we found that the aptamer library employed here required more than 15 rounds of in vivo selection for convergence to specific sequences. The aptamer species identified through this approach bound to brain capillary endothelia and penetrated into the parenchyma. The methods described may find general utility for targeting various payloads to the brain. PMID:23299833
Ramlal, Shylaja; Mondal, Bhairab; Lavu, Padma Sudharani; N, Bhavanashri; Kingston, Joseph
2018-01-16
In the present study, a high throughput whole cell SELEX method has been applied successfully in selecting specific aptamers against whole cells of Staphylococcus aureus, a potent food poisoning bacterium. A total ten rounds of SELEX and three rounds of intermittent counter SELEX, was performed to obtain specific aptamers. Obtained oligonucleotide pool were cloned, sequenced and then grouped into different families based on their primary sequence homology and secondary structure similarity. FITC labeled sequences from different families were selected for further characterization via flow cytometry analysis. The dissociation constant (K d ) values of specific and higher binders ranged from 34 to 128nM. Binding assays to assess the selectivity of aptamer RAB10, RAB 20, RAB 28 and RAB 35 demonstrated high affinity against S. aureus and low binding affinity for other bacteria. To demonstrate the potential use of the aptamer a sensitive dual labeled sandwich detection system was developed using aptamer RAB10 and RAB 35 with a detection limit of 10 2 CFU/mL. Furthermore detection from mixed cell population and spiked sample emphasized the robustness as well as applicability of the developed method. Altogether, the established assay could be a reliable detection tool for the routine investigation of Staphylococcus aureus in samples from food and clinical sources. Copyright © 2017. Published by Elsevier B.V.
Singh, Naveen Kumar; Chakma, Babina; Jain, Priyamvada; Goswami, Pranab
2018-06-11
A novel 90-mer long ssDNA aptamer (NG3) covering a 40-mer random region targeting Plasmodium falciparum glutamate dehydrogenase ( PfGDH) developed through systematic evolution of ligands by exponential enrichment (SELEX) technique. The binding affinity of the aptamer to PfGDH discerned by circular dichroism (CD) was 0.5 ± 0.04 μM. The specificity of the aptamer toward the target was confirmed by gel electrophoresis and CD studies. The presence of two quadruplex forming regions, two big and four small stem loop structures with a δG of -7.99 kcal mol -1 for NG3 were deduced by computational studies. The spherical carbon dots (Cdots) of size 2-4 nm, synthesized by pyrolysis method using l-glutamate as a substrate were covalently linked to the amine modified aptamer. The Cdot with a band gap of 2.8 eV and a quantum yield of 34% produced fluorescence at ∼ λ 410 nm when excited at λ 320nm . The quantum yield of Cdot-aptamer assembly was increased up to 40% in the presence of the PfGDH in solution. A linear relationship with a dynamic range of 0.5 nM to 25 nM (R 2 = 0.98) and a limit of detection (LOD) of 0.48 nM was observed between the fluorescence intensity of the Cdots-aptamer conjugate and the concentration of PfGDH. The method could detect PfGDH with an LOD of 2.85 nM in diluted serum sample. This novel simple, sensitive and specific protein induced fluorescence enhancement based detection of PfGDH has a great potential to develop as a method for malaria detection.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Deng-Liang; Department of Neurosurgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou; Song, Yan-Ling
2014-10-31
Highlights: • This is the first report of DNA aptamer against EGFR in vitro. • Aptamer can bind targets with high affinity and selectivity. • DNA aptamers are more stable, cheap and efficient than RNA aptamers. • Our selected DNA aptamer against EGFR has high affinity with K{sub d} 56 ± 7.3 nM. • Our selected DNA aptamer against EGFR has high selectivity. - Abstract: Epidermal growth factor receptor (EGFR/HER1/c-ErbB1), is overexpressed in many solid cancers, such as epidermoid carcinomas, malignant gliomas, etc. EGFR plays roles in proliferation, invasion, angiogenesis and metastasis of malignant cancer cells and is the idealmore » antigen for clinical applications in cancer detection, imaging and therapy. Aptamers, the output of the systematic evolution of ligands by exponential enrichment (SELEX), are DNA/RNA oligonucleotides which can bind protein and other substances with specificity. RNA aptamers are undesirable due to their instability and high cost of production. Conversely, DNA aptamers have aroused researcher’s attention because they are easily synthesized, stable, selective, have high binding affinity and are cost-effective to produce. In this study, we have successfully identified DNA aptamers with high binding affinity and selectivity to EGFR. The aptamer named TuTu22 with K{sub d} 56 ± 7.3 nM was chosen from the identified DNA aptamers for further study. Flow cytometry analysis results indicated that the TuTu22 aptamer was able to specifically recognize a variety of cancer cells expressing EGFR but did not bind to the EGFR-negative cells. With all of the aforementioned advantages, the DNA aptamers reported here against cancer biomarker EGFR will facilitate the development of novel targeted cancer detection, imaging and therapy.« less
Coma dust environment observed by GIADA during the Perihelion of 67P/Churyumov-Gerasimenko.
NASA Astrophysics Data System (ADS)
Rotundi, A.; Della Corte, V.; Fulle, M.; Ferrari, M.; Ivanovski, S. L.; Sordini, R.; Mazzotta Epifani, E.; Palumbo, P.; Colangeli, L.; Lopez-Moreno, J. J.; Rodriguez, J.; Zakharov, V.; Bussoletti, E.; Crifo, J. F.; Esposito, F.; Green, S.; Gruen, E.; Lamy, P. L.; McDonnell, T.; Mennella, V.; Molina, A.; Moreno, F.; Ortiz, J. L.; Palomba, E.; Perrin, J. M.; Rodrigo, R.; Weissman, P. R.; Zarnecki, J.; Cosi, M.; Giovane, F.; Gustafson, B.; Herranz, M.; Jeronimo, J. M.; Leese, M.; Lopez-Jimenez, A.; Morales, R.
2015-12-01
GIADA (Grain Impact Analyzer and Dust Accumulator) is an in-situ instrument mounted onboard Rosetta monitoring the dust environment of comet 67P/Churyumov-Gerasimenko. GIADA is composed of 3 sub-systems: 1) the Grain Detection System, based on particle detection through light scattering; 2) the Impact Sensor, giving momentum measurement; 3) the Micro-Balances System, constituted of 5 quartz crystal microbalances, giving cumulative deposited dust. The combination of the measurements performed by these 3 subsystems provides: the number, the mass, the momentum and the speed distribution of dust particles emitted from the comet nucleus. We will present the coma dust environment as observed by GIADA during the perihelion phase of the Rosetta space mission. Despite the large distance from the nucleus, more than 200 km, GIADA was able to detect temporal and spatial variation of dust density distribution. Specific high dust spatial density sectors of the coma have been identified and their evolution during the perihelion phase was studied. Acknowledgements. GIADA was built by a consortium led by the Univ. Napoli "Parthenope" & INAF- Oss. Astr. Capodimonte, IT, in collaboration with the Inst. de Astrofisica de Andalucia, ES, Selex-ES s.p.a. and SENER. GIADA is presently managed & operated by Ist. di Astrofisica e Planetologia Spaziali-INAF, IT. GIADA was funded and managed by the Agenzia Spaziale Italiana, IT, with a support of the Spanish Ministry of Education and Science MEC, ES. GIADA was developped from a PI proposal supported by the University of Kent; sci. & tech. contribution given by CISAS, IT, Lab. d'Astr. Spat., FR, and Institutions from UK, IT, FR, DE and USA. We thank the RSGS/ESAC, RMOC/ESOC & Rosetta Project/ESTEC for their outstanding work. Science support provided by NASA through the US Rosetta Project managed by JPL/California Institute of Technology. GIADA calibrated data will be available through the ESA's PSA web site.
OnTheFly: a database of Drosophila melanogaster transcription factors and their binding sites.
Shazman, Shula; Lee, Hunjoong; Socol, Yakov; Mann, Richard S; Honig, Barry
2014-01-01
We present OnTheFly (http://bhapp.c2b2.columbia.edu/OnTheFly/index.php), a database comprising a systematic collection of transcription factors (TFs) of Drosophila melanogaster and their DNA-binding sites. TFs predicted in the Drosophila melanogaster genome are annotated and classified and their structures, obtained via experiment or homology models, are provided. All known preferred TF DNA-binding sites obtained from the B1H, DNase I and SELEX methodologies are presented. DNA shape parameters predicted for these sites are obtained from a high throughput server or from crystal structures of protein-DNA complexes where available. An important feature of the database is that all DNA-binding domains and their binding sites are fully annotated in a eukaryote using structural criteria and evolutionary homology. OnTheFly thus provides a comprehensive view of TFs and their binding sites that will be a valuable resource for deciphering non-coding regulatory DNA.
Aptamer-Based Paper Strip Sensor for Detecting Vibrio fischeri.
Shin, Woo-Ri; Sekhon, Simranjeet Singh; Rhee, Sung-Keun; Ko, Jung Ho; Ahn, Ji-Young; Min, Jiho; Kim, Yang-Hoon
2018-05-14
Aptamer-based paper strip sensor for detecting Vibrio fischeri was developed. Our method was based on the aptamer sandwich assay between whole live cells, V. fischeri and DNA aptamer probes. Following 9 rounds of Cell-SELEX and one of the negative-SELEX, V. fischeri Cell Aptamer (VFCA)-02 and -03 were isolated, with the former showing approximately 10-fold greater avidity (in the subnanomolar range) for the target cells when arrayed on a surface. The colorimetric response of a paper sensor based on VFCA-02 was linear in the range of 4 × 10 1 to 4 × 10 5 CFU/mL of target cell by using scanning reader. The linear regression correlation coefficient ( R 2 ) was 0.9809. This system shows promise for use in aptamer-conjugated gold nanoparticle probes in paper strip format for in-field detection of marine bioindicating bacteria.
Feng, Hui; Beck, Jürgen; Nassal, Michael; Hu, Kang-hong
2011-01-01
Background The specific interaction between hepatitis B virus (HBV) polymerase (P protein) and the ε RNA stem-loop on pregenomic (pg) RNA is crucial for viral replication. It triggers both pgRNA packaging and reverse transcription and thus represents an attractive antiviral target. RNA decoys mimicking ε in P protein binding but not supporting replication might represent novel HBV inhibitors. However, because generation of recombinant enzymatically active HBV polymerase is notoriously difficult, such decoys have as yet not been identified. Methodology/Principal Findings Here we used a SELEX approach, based on a new in vitro reconstitution system exploiting a recombinant truncated HBV P protein (miniP), to identify potential ε decoys in two large ε RNA pools with randomized upper stem. Selection of strongly P protein binding RNAs correlated with an unexpected strong enrichment of A residues. Two aptamers, S6 and S9, displayed particularly high affinity and specificity for miniP in vitro, yet did not support viral replication when part of a complete HBV genome. Introducing S9 RNA into transiently HBV producing HepG2 cells strongly suppressed pgRNA packaging and DNA synthesis, indicating the S9 RNA can indeed act as an ε decoy that competitively inhibits P protein binding to the authentic ε signal on pgRNA. Conclusions/Significance This study demonstrates the first successful identification of human HBV ε aptamers by an in vitro SELEX approach. Effective suppression of HBV replication by the S9 aptamer provides proof-of-principle for the ability of ε decoy RNAs to interfere with viral P-ε complex formation and suggests that S9-like RNAs may further be developed into useful therapeutics against chronic hepatitis B. PMID:22125633
Technical Communications in Urban Operations (Les communications techniques en operations urbaines)
2010-09-01
SCUTI – Scuola Trasmissioni ed Informatica dell’Esercito Italiano Via dei Genieri, 287, 00143-Roma Cecchignola Email: Mario.DiStefano@selex...comms.com Lt. Fabrizio LAMBIASE SCUTI – Scuola Trasmissioni ed Informatica dell’Esercito Italiano Via dei Genieri, 287, 00143 Roma Cecchignola
Dua, Pooja; Kang, Sinae; Shin, Hye-Soo; Kim, Soyoun; Lee, Dong-Ki
2018-04-02
Increased interest and insights gained by researchers on the roles of endothelial cells in the pathophysiology of cancer, inflammatory, and cardiovascular diseases have led to the design of pharmacological interventions aimed at the endothelium lining in the diseased sites. Toward this end, we used established brain microvascular endothelial cell lines mouse (bEND3), human (hCMEC/D3), and Toggle Cell-SELEX to identify a species cross-reactive, endothelial cell-internalizing aptamer R11-3. This 2'F-modified RNA aptamer is specific for endothelial cells as no internalization was seen with cells of nonendothelial origin. R11-3 was truncated in size, and its potential in endothelial targeted therapeutics was established using VEGFR2 targeting long interfering RNA (liRNA) aptamer chimera. Due to its specificity for both mouse and human endothelial cells, we believe that this aptamer not only fits for development of endothelial targeted drug development for human diseases but is also suitable for preclinical evaluation in mice.
Selection of a high-affinity and in vivo bioactive ssDNA aptamer against angiotensin II peptide.
Heiat, Mohammad; Ranjbar, Reza; Latifi, Ali Mohammad; Rasaee, Mohammad Javad
2016-08-01
Unique features of aptamers have attracted interests for a broad range of applications. Aptamers are able to specifically bind to targets and inhibit their functions. This study, aimed to isolate the high affinity ssDNA aptamers against bio-regulator peptide angiotensin II (Ang II) and investigate their bioactivity in cellular and animal models. To isolate ssDNA aptamers, 12 rounds of affinity chromatography SELEX (Systematic Evolution of Ligands by EXponential enrichment) procedure were carried out. The SPR (surface plasmon resonance) and ELONA (enzyme linked oligonucleotide assay) analysis were used to determine the affinity and specificity of aptamers. The ability of selected aptamers to inhibit the proliferative effect of Ang II on human aortic vascular smooth muscle cells (HA-VSMCs) and their performance on Wistar rat urinary system and serum electrolyte levels were investigated. Two full-length aptamers (FLC112 and FLC125) with high affinity of respectively 7.52±2.44E-10 and 5.87±1.3E-9M were isolated against Ang II. The core regions of these aptamers (CRC112 and CRC125) also showed affinity of 5.33±1.15E-9 and 4.11±1.09E-9M. In vitro analysis revealed that FLC112 and FLC125 can inhibit the proliferative effect of Ang II on HA-VSMCs (P<0.05). They also significantly reduced the serum sodium level and increased the urine volume (P<0.05). The core regions of aptamers did not show high inhibitory potential against Ang II. It can be a spotlight that ssDNA aptamers have high potential for blocking Ang II. In conclusion, it appears that the researches focusing on high affinity and bioactive aptamers may lead to excellent results in blocking Ang II activity. Copyright © 2016 Elsevier Inc. All rights reserved.
Li, Shaohua; Li, Hui; Yang, Xiqin; Wang, Wei; Huang, Aixue; Li, Jie; Qin, Xingliang; Li, Fei; Lu, Guanyi; Ding, Hongmei; Su, Xueting; Hou, Lvbin; Xia, Wei; Shi, Ming; Zhang, Hongwen; Zhao, Qiang; Dong, Jie; Ge, Xingfeng; Sun, Leqiao; Bai, Chenjun; Wang, Chaonan; Shen, Xuelian; Fang, Tao; Wang, Fusheng; Zhang, Heqiu; Shao, Ningsheng
2015-04-30
We report a new biomarker of hepatocarcinoma, vasorin (VASN), screened by a subtractive EMSA-SELEX strategy from AFP negative serum of hepatocellular carcinoma (HCC) patients with extrahepatic metastases. VASN was verified to be highly expressed in sera of 100 cases of HCC patients compared with 97 cases of normal persons and 129 cases of hepatitis patients. Further validation by Q-PCR,IFA and Western blot showed higher expression of VASN at mRNA and protein levels in HCC cell lines and HCC tissues than in normal controls. RNA interference and forced overexpression assays verified that VASN promotes cell proliferation and migration and inhibits apoptosis. Down-regulation of microRNA miR145 and miR146a is an important mechanism leading to high expression of VASN. As a membrane protein and/or as free protein, VASN may be an effective target for biological treatment of liver cancer and is a potential biomarker for HCC diagnosis. Small molecular nucleotides targeting VASN are promising biological therapies to HCC.
Wang, Wei; Huang, Aixue; Li, Jie; Qin, Xingliang; Li, Fei; Lu, Guanyi; Ding, Hongmei; Su, Xueting; Hou, Lvbin; Xia, Wei; Shi, Ming; Zhang, Hongwen; Zhao, Qiang; Dong, Jie; Ge, Xingfeng; Sun, Leqiao; Bai, Chenjun; Wang, Chaonan; Shen, Xuelian; Fang, Tao; Wang, Fusheng; Zhang, Heqiu; Shao, Ningsheng
2015-01-01
We report a new biomarker of hepatocarcinoma, vasorin (VASN), screened by a subtractive EMSA-SELEX strategy from AFP negative serum of hepatocellular carcinoma (HCC) patients with extrahepatic metastases. VASN was verified to be highly expressed in sera of 100 cases of HCC patients compared with 97 cases of normal persons and 129 cases of hepatitis patients. Further validation by Q-PCR, IFA and Western blot showed higher expression of VASN at mRNA and protein levels in HCC cell lines and HCC tissues than in normal controls. RNA interference and forced overexpression assays verified that VASN promotes cell proliferation and migration and inhibits apoptosis. Down-regulation of microRNA miR145 and miR146a is an important mechanism leading to high expression of VASN. Conclusion: As a membrane protein and/or as free protein, VASN may be an effective target for biological treatment of liver cancer and is a potential biomarker for HCC diagnosis. Small molecular nucleotides targeting VASN are promising biological therapies to HCC. PMID:25826090
Chen, Dana; Orenstein, Yaron; Golodnitsky, Rada; Pellach, Michal; Avrahami, Dorit; Wachtel, Chaim; Ovadia-Shochat, Avital; Shir-Shapira, Hila; Kedmi, Adi; Juven-Gershon, Tamar; Shamir, Ron; Gerber, Doron
2016-01-01
Transcription factors (TFs) alter gene expression in response to changes in the environment through sequence-specific interactions with the DNA. These interactions are best portrayed as a landscape of TF binding affinities. Current methods to study sequence-specific binding preferences suffer from limited dynamic range, sequence bias, lack of specificity and limited throughput. We have developed a microfluidic-based device for SELEX Affinity Landscape MAPping (SELMAP) of TF binding, which allows high-throughput measurement of 16 proteins in parallel. We used it to measure the relative affinities of Pho4, AtERF2 and Btd full-length proteins to millions of different DNA binding sites, and detected both high and low-affinity interactions in equilibrium conditions, generating a comprehensive landscape of the relative TF affinities to all possible DNA 6-mers, and even DNA10-mers with increased sequencing depth. Low quantities of both the TFs and DNA oligomers were sufficient for obtaining high-quality results, significantly reducing experimental costs. SELMAP allows in-depth screening of hundreds of TFs, and provides a means for better understanding of the regulatory processes that govern gene expression. PMID:27628341
DEAF-1 regulates immunity gene expression in Drosophila.
Reed, Darien E; Huang, Xinhua M; Wohlschlegel, James A; Levine, Michael S; Senger, Kate
2008-06-17
Immunity genes are activated in the Drosophila fat body by Rel and GATA transcription factors. Here, we present evidence that an additional regulatory factor, deformed epidermal autoregulatory factor-1 (DEAF-1), also contributes to the immune response and is specifically important for the induction of two genes encoding antimicrobial peptides, Metchnikowin (Mtk) and Drosomycin (Drs). The systematic mutagenesis of a minimal Mtk 5' enhancer identified a sequence motif essential for both a response to LPS preparations in S2 cells and activation in the larval fat body in response to bacterial infection. Using affinity chromatography coupled to multidimensional protein identification technology (MudPIT), we identified DEAF-1 as a candidate regulator. DEAF-1 activates the expression of Mtk and Drs promoter-luciferase fusion genes in S2 cells. SELEX assays and footprinting data indicate that DEAF-1 binds to and activates Mtk and Drs regulatory DNAs via a TTCGGBT motif. The insertion of this motif into the Diptericin (Dpt) regulatory region confers DEAF-1 responsiveness to this normally DEAF-1-independent enhancer. The coexpression of DEAF-1 with Dorsal, Dif, and Relish results in the synergistic activation of transcription. We propose that DEAF-1 is a regulator of Drosophila immunity.
[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.
Advancements in Aptamer Discovery Technologies.
Gotrik, Michael R; Feagin, Trevor A; Csordas, Andrew T; Nakamoto, Margaret A; Soh, H Tom
2016-09-20
Affinity reagents that specifically bind to their target molecules are invaluable tools in nearly every field of modern biomedicine. Nucleic acid-based aptamers offer many advantages in this domain, because they are chemically synthesized, stable, and economical. Despite these compelling features, aptamers are currently not widely used in comparison to antibodies. This is primarily because conventional aptamer-discovery techniques such as SELEX are time-consuming and labor-intensive and often fail to produce aptamers with comparable binding performance to antibodies. This Account describes a body of work from our laboratory in developing advanced methods for consistently producing high-performance aptamers with higher efficiency, fewer resources, and, most importantly, a greater probability of success. We describe our efforts in systematically transforming each major step of the aptamer discovery process: selection, analysis, and characterization. To improve selection, we have developed microfluidic devices (M-SELEX) that enable discovery of high-affinity aptamers after a minimal number of selection rounds by precisely controlling the target concentration and washing stringency. In terms of improving aptamer pool analysis, our group was the first to use high-throughput sequencing (HTS) for the discovery of new aptamers. We showed that tracking the enrichment trajectory of individual aptamer sequences enables the identification of high-performing aptamers without requiring full convergence of the selected aptamer pool. HTS is now widely used for aptamer discovery, and open-source software has become available to facilitate analysis. To improve binding characterization, we used HTS data to design custom aptamer arrays to measure the affinity and specificity of up to ∼10(4) DNA aptamers in parallel as a means to rapidly discover high-quality aptamers. Most recently, our efforts have culminated in the invention of the "particle display" (PD) screening system, which transforms solution-phase aptamers into "aptamer particles" that can be individually screened at high-throughput via fluorescence-activated cell sorting. Using PD, we have shown the feasibility of rapidly generating aptamers with exceptional affinities, even for proteins that have previously proven intractable to aptamer discovery. We are confident that these advanced aptamer-discovery methods will accelerate the discovery of aptamer reagents with excellent affinities and specificities, perhaps even exceeding those of the best monoclonal antibodies. Since aptamers are reproducible, renewable, stable, and can be distributed as sequence information, we anticipate that these affinity reagents will become even more valuable tools for both research and clinical applications.
Federal Register 2010, 2011, 2012, 2013, 2014
2011-12-23
...; SignalCore Inc., Austin, TX; Modular Methods, LLC, Steamboat Springs, CO; and SELEX Galileo S.p.A., Roma... DEPARTMENT OF JUSTICE Antitrust Division Notice Pursuant to the National Cooperative Research and..., pursuant to Section 6(a) of the National Cooperative Research and Production Act of 1993, 15 U.S.C. 4301 et...
Nanobioprobe mediated DNA aptamers for explosive detection.
Priyanka; Shorie, Munish; Bhalla, Vijayender; Pathania, Preeti; Suri, C Raman
2014-02-04
Specific nucleic acid aptamers using the microtiter plate based modified SELEX method against explosive trinitrotoluene are reported. Efficient partitioning of dsDNA was carried out using streptavidin labeled gold nanoprobes for the selection of specific aptamers. The selected binders having an affinity of ~10(-7) M were used in the newly developed electrochemical aptasensor, exhibiting a detection limit of around 1 ppb for trinitrotoluene.
Engineering modular ‘ON’ RNA switches using biological components
Ceres, Pablo; Trausch, Jeremiah J.; Batey, Robert T.
2013-01-01
Riboswitches are cis-acting regulatory elements broadly distributed in bacterial mRNAs that control a wide range of critical metabolic activities. Expression is governed by two distinct domains within the mRNA leader: a sensory ‘aptamer domain’ and a regulatory ‘expression platform’. Riboswitches have also received considerable attention as important tools in synthetic biology because of their conceptually simple structure and the ability to obtain aptamers that bind almost any conceivable small molecule using in vitro selection (referred to as SELEX). In the design of artificial riboswitches, a significant hurdle has been to couple the two domains enabling their efficient communication. We previously demonstrated that biological transcriptional ‘OFF’ expression platforms are easily coupled to diverse aptamers, both biological and SELEX-derived, using simple design rules. Here, we present two modular transcriptional ‘ON’ riboswitch expression platforms that are also capable of hosting foreign aptamers. We demonstrate that these biological parts can be used to facilely generate artificial chimeric riboswitches capable of robustly regulating transcription both in vitro and in vivo. We expect that these modular expression platforms will be of great utility for various synthetic biological applications that use RNA-based biosensors. PMID:23999097
Lee, Kyue Yim; Kang, Hyungu; Ryu, Sung Ho; Lee, Dong Soo; Lee, Jung Hwan; Kim, Soonhag
2010-01-01
Chemically modified nucleotides have been developed and applied into SELEX procedure to find a novel type of aptamers to fit with targets of interest. In this study, we directly performed chemical modification of 5-(N-benzylcarboxyamide)-2′-deoxyuridine (called 5-BzdU) in the AS1411 aptamer, which binds to the nucleolin protein expressed in cancer cells. Forty-seven compounds of AS1411-containing Cy3-labeled 5-BzdU (called Cy3-(5-BzdU)-modified-AS1411) were synthesized by randomly substituting thymidines one to twelve in AS1411 with Cy3-labeled 5-BzdU. Both statistically quantified fluorescence measurements and confocal imaging analysis demonstrated at least three potential compounds of interest: number 12, 29 and 41 that significantly increased the targeting affinity to cancer cells but no significant activity from normal healthy cells. These results suggest that the position and number of substituents in AS1411 are critical parameters to improve the aptamer function. In this study, we demonstrated that chemical modification of the existing aptamers enhanced the binding and targeting affinity to targets of interest without additional SELEX procedures. PMID:20204158
NASA Astrophysics Data System (ADS)
Della Corte, Vincenzo; Rotundi, Alessandra; Fulle, Marco
2016-07-01
GIADA (Grain Impact Analyzer and Dust Accumulator) is an in-situ instrument onboard Rosetta monitoring the dust environment of comet 67P/Churyumov-Gerasimenko. GIADA is composed of 3 sub-systems: 1) the Grain Detection System, based on particle detection through light scattering; 2) the Impact Sensor, measuring particle momentum; 3) the Micro-Balances System, constituted of 5 quartz crystal microbalances, providing cumulated dust from different directions. From the combination of the measurements performed by the three subsystems we retrieve: the number, the mass, the momentum, the speed of individual dust particles and the cumulative dust flux emitted from the comet nucleus. We will present the coma dust environment as observed by GIADA during the pre-landing and escort phases of the Rosetta space mission. GIADA was able to detect temporal and spatial variation of dust density distribution and to disentangle different types of impacting dust particles. Specific high dust spatial density sectors of the coma have been identified and their evolution with respect to the heliocentric distance was studied. From August 2014 to December 2015, i.e. inbound, at and outbound perihelion, Rosetta performed different trajectories around the nucleus and flybys with different close approach distances, different coordinates of the sub-spacecraft point and different observing geometry (phase angle), allowed GIADA to characterize the dust environment within the 67P/C-G coma and its temporal variation. Acknowledgements. GIADA was built by a consortium led by the Univ. Napoli "Parthenope" & INAF- Oss. Astr. Capodimonte, IT, in collaboration with the Inst. de Astrofisica de Andalucia, ES, Selex-ES s.p.a. and SENER. GIADA is presently managed & operated by Ist. di Astrofisica e Planetologia Spaziali-INAF, IT. GIADA was funded and managed by the Agenzia Spaziale Italiana, IT, with a support of the Spanish Ministry of Education and Science MEC, ES. GIADA was developed from a PI proposal supported by the University of Kent; sci. & tech. contribution given by CISAS, IT, Lab. d'Astr. Spat., FR, and Institutions from UK, IT, FR, DE and USA. We thank the RSGS/ESAC, RMOC/ESOC & Rosetta Project/ESTEC for their outstanding work. Science support provided by NASA through the US Rosetta Project managed by JPL/California Institute of Technology. GIADA calibrated data will be available through the ESA's PSA web site.
Frequency of RNA–RNA interaction in a model of the RNA World
STRIGGLES, JOHN C.; MARTIN, MATTHEW B.; SCHMIDT, FRANCIS J.
2006-01-01
The RNA World model for prebiotic evolution posits the selection of catalytic/template RNAs from random populations. The mechanisms by which these random populations could be generated de novo are unclear. Non-enzymatic and RNA-catalyzed nucleic acid polymerizations are poorly processive, which means that the resulting short-chain RNA population could contain only limited diversity. Nonreciprocal recombination of smaller RNAs provides an alternative mechanism for the assembly of larger species with concomitantly greater structural diversity; however, the frequency of any specific recombination event in a random RNA population is limited by the low probability of an encounter between any two given molecules. This low probability could be overcome if the molecules capable of productive recombination were redundant, with many nonhomologous but functionally equivalent RNAs being present in a random population. Here we report fluctuation experiments to estimate the redundancy of the set of RNAs in a population of random sequences that are capable of non-Watson-Crick interaction with another RNA. Parallel SELEX experiments showed that at least one in 106 random 20-mers binds to the P5.1 stem–loop of Bacillus subtilis RNase P RNA with affinities equal to that of its naturally occurring partner. This high frequency predicts that a single RNA in an RNA World would encounter multiple interacting RNAs within its lifetime, supporting recombination as a plausible mechanism for prebiotic RNA evolution. The large number of equivalent species implies that the selection of any single interacting species in the RNA World would be a contingent event, i.e., one resulting from historical accident. PMID:16495233
Escudero-Abarca, Blanca I.; Suh, Soo Hwan; Moore, Matthew D.; Dwivedi, Hari P.; Jaykus, Lee-Ann
2014-01-01
Human noroviruses (HuNoV) are the leading cause of acute viral gastroenteritis and an important cause of foodborne disease. Despite their public health significance, routine detection of HuNoV in community settings, or food and environmental samples, is limited, and there is a need to develop alternative HuNoV diagnostic reagents to complement existing ones. The purpose of this study was to select and characterize single-stranded (ss)DNA aptamers with binding affinity to HuNoV. The utility of these aptamers was demonstrated in their use for capture and detection of HuNoV in outbreak-derived fecal samples and a representative food matrix. SELEX (Systematic Evolution of Ligands by EXponential enrichment) was used to isolate ssDNA aptamer sequences with broad reactivity to the prototype GII.2 HuNoV strain, Snow Mountain Virus (SMV). Four aptamer candidates (designated 19, 21, 25 and 26) were identified and screened for binding affinity to 14 different virus-like particles (VLPs) corresponding to various GI and GII HuNoV strains using an Enzyme-Linked Aptamer Sorbant Assay (ELASA). Collectively, aptamers 21 and 25 showed affinity to 13 of the 14 VLPs tested, with strongest binding to GII.2 (SMV) and GII.4 VLPs. Aptamer 25 was chosen for further study. Its binding affinity to SMV-VLPs was equivalent to that of a commercial antibody within a range of 1 to 5 µg/ml. Aptamer 25 also showed binding to representative HuNoV strains present in stool specimens obtained from naturally infected individuals. Lastly, an aptamer magnetic capture (AMC) method using aptamer 25 coupled with RT-qPCR was developed for recovery and detection of HuNoV in artificially contaminated lettuce. The capture efficiency of the AMC was 2.5–36% with an assay detection limit of 10 RNA copies per lettuce sample. These ssDNA aptamer candidates show promise as broadly reactive reagents for use in HuNoV capture and detection assays in various sample types. PMID:25192421
Introduction to Radar Signal and Data Processing: The Opportunity
2006-09-01
SpA) Director of Analysis of Integrated Systems Group Via Tiburtina Km. 12.400 00131 Rome ITALY e.mail: afarina@selex-si.com Key words: radar...signal processing, data processing, adaptivity, space-time adaptive processing, knowledge based systems , CFAR. 1. SUMMARY This paper introduces to...the lecture series dedicated to the knowledge-based radar signal and data processing. Knowledge-based expert system (KBS) is in the realm of
Infrared sensors for Earth observation missions
NASA Astrophysics Data System (ADS)
Ashcroft, P.; Thorne, P.; Weller, H.; Baker, I.
2007-10-01
SELEX S&AS is developing a family of infrared sensors for earth observation missions. The spectral bands cover shortwave infrared (SWIR) channels from around 1μm to long-wave infrared (LWIR) channels up to 15μm. Our mercury cadmium telluride (MCT) technology has enabled a sensor array design that can satisfy the requirements of all of the SWIR and medium-wave infrared (MWIR) bands with near-identical arrays. This is made possible by the combination of a set of existing technologies that together enable a high degree of flexibility in the pixel geometry, sensitivity, and photocurrent integration capacity. The solution employs a photodiode array under the control of a readout integrated circuit (ROIC). The ROIC allows flexible geometries and in-pixel redundancy to maximise operability and reliability, by combining the photocurrent from a number of photodiodes into a single pixel. Defective or inoperable diodes (or "sub-pixels") can be deselected with tolerable impact on the overall pixel performance. The arrays will be fabricated using the "loophole" process in MCT grown by liquid-phase epitaxy (LPE). These arrays are inherently robust, offer high quantum efficiencies and have been used in previous space programs. The use of loophole arrays also offers access to SELEX's avalanche photodiode (APD) technology, allowing low-noise, highly uniform gain at the pixel level where photon flux is very low.
Brozovic, Matija; Dantec, Christelle; Dardaillon, Justine; Dauga, Delphine; Faure, Emmanuel; Gineste, Mathieu; Louis, Alexandra; Naville, Magali; Nitta, Kazuhiro R; Piette, Jacques; Reeves, Wendy; Scornavacca, Céline; Simion, Paul; Vincentelli, Renaud; Bellec, Maelle; Aicha, Sameh Ben; Fagotto, Marie; Guéroult-Bellone, Marion; Haeussler, Maximilian; Jacox, Edwin; Lowe, Elijah K; Mendez, Mickael; Roberge, Alexis; Stolfi, Alberto; Yokomori, Rui; Cambillau, Christian; Christiaen, Lionel; Delsuc, Frédéric; Douzery, Emmanuel; Dumollard, Rémi; Kusakabe, Takehiro; Nakai, Kenta; Nishida, Hiroki; Satou, Yutaka; Swalla, Billie; Veeman, Michael; Volff, Jean-Nicolas
2018-01-01
Abstract ANISEED (www.aniseed.cnrs.fr) is the main model organism database for tunicates, the sister-group of vertebrates. This release gives access to annotated genomes, gene expression patterns, and anatomical descriptions for nine ascidian species. It provides increased integration with external molecular and taxonomy databases, better support for epigenomics datasets, in particular RNA-seq, ChIP-seq and SELEX-seq, and features novel interactive interfaces for existing and novel datatypes. In particular, the cross-species navigation and comparison is enhanced through a novel taxonomy section describing each represented species and through the implementation of interactive phylogenetic gene trees for 60% of tunicate genes. The gene expression section displays the results of RNA-seq experiments for the three major model species of solitary ascidians. Gene expression is controlled by the binding of transcription factors to cis-regulatory sequences. A high-resolution description of the DNA-binding specificity for 131 Ciona robusta (formerly C. intestinalis type A) transcription factors by SELEX-seq is provided and used to map candidate binding sites across the Ciona robusta and Phallusia mammillata genomes. Finally, use of a WashU Epigenome browser enhances genome navigation, while a Genomicus server was set up to explore microsynteny relationships within tunicates and with vertebrates, Amphioxus, echinoderms and hemichordates. PMID:29149270
Measurement of the cross section of charmed hadrons and the nuclear dependence alpha (in Spanish)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Blanco-Covarrubias, Ernesto Alejandro
2009-12-03
With data from the SELEX experiment we study charm hadro-production. We report the differential production cross sections as function of the longitudinal and transverse momentum, as well as for two different target materials, of 14 charmed hadron and/or their decay modes. This is the most extensive study to date. SELEX is a fixed target experiment at Fermilab with high forward acceptance; it took data during 1996-1997 with 600 GeV/c Σ - and π -, and 540 GeV/c proton and π + beams. It used 5 target foils (two copper and three diamond). We use the results to determine α, usedmore » in parametrizing the production cross section as ∞ A α, where A is the mass number of the target nuclei. We found within our statistics that α is independent of the longitudinal momentum fraction x F in the interval 0.1 < x F < 1.0, with α = 0.778 ± 0.014. The average value of α} for charm production by pion beams is α meson = 0.850 ± 0.028. This is somewhat larger than the corresponding average α baryon = 0.755 ± 0.016 for charm production by baryon beams (Σ - and protons).« less
Quantum efficiency performances of the NIR European Large Format Array detectors tested at ESTEC
NASA Astrophysics Data System (ADS)
Crouzet, P.-E.; Duvet, L.; de Wit, F.; Beaufort, T.; Blommaert, S.; Butler, B.; Van Duinkerken, G.; ter Haar, J.; Heijnen, J.; van der Luijt, K.; Smit, H.
2015-10-01
Publisher's Note: This paper, originally published on 10/12/2015, was replaced with a corrected/revised version on 10/23/2015. If you downloaded the original PDF but are unable to access the revision, please contact SPIE Digital Library Customer Service for assistance. The Payload Technology Validation Section (SRE-FV) at ESTEC has the goal to validate new technology for future or on-going mission. In this framework, a test set up to characterize the quantum efficiency of near-infrared (NIR) detectors has been created. In the context of the NIR European Large Format Array ("LFA"), 3 deliverables detectors coming from SELEX-UK/ATC (UK) on one side, and CEA/LETI- CEA/IRFU-SOFRADIR (FR) on the other side were characterized. The quantum efficiency of an HAWAII-2RG detector from Teledyne was as well measured. The capability to compare on the same setup detectors from different manufacturers is a unique asset for the future mission preparation office. This publication will present the quantum efficiency results of a HAWAII-2RG detector from Teledyne with a 2.5um cut off compared to the LFA European detectors prototypes developed independently by SELEX-UK/ATC (UK) on one side, and CEA/LETI- CEA/IRFU-SOFRADIR (FR) on the other side.
Building a complete image of genome regulation in the model organism Escherichia coli.
Ishihama, Akira
2018-01-15
The model organism, Escherichia coli, contains a total of more than 4,500 genes, but the total number of RNA polymerase (RNAP) core enzyme or the transcriptase is only about 2,000 molecules per genome. The regulatory targets of RNAP are, however, modulated by changing its promoter selectivity through two-steps of protein-protein interplay with 7 species of the sigma factor in the first step, and then 300 species of the transcription factor (TF) in the second step. Scientists working in the field of prokaryotic transcription in Japan have made considerable contributions to the elucidation of genetic frameworks and regulatory modes of the genome transcription in E. coli K-12. This review summarizes the findings by this group, first focusing on three sigma factors, the stationary-phase sigma RpoS, the heat-shock sigma RpoH, and the flagellar-chemotaxis sigma RpoF, as examples. It also presents an overview of the current state of the systematic research being carried out to identify the regulatory functions of all TFs from a single and the same bacterium E. coli K-12, using the genomic SELEX and PS-TF screening systems. All these studies have been undertaken with the aim of understanding the genome regulation in E. coli K-12 as a whole.
Development of highly compact and low power consumption athermal military laser designators
NASA Astrophysics Data System (ADS)
Sijan, A.
2012-10-01
The utility of military lasers, particularly in the area of laser designation for laser-guided weapons, is well understood. Laser systems based on Nd:YAG have been fielded since the 1980's and over the last three decades have introduced incremental technology steps to improve performance and weight. The most recent technology step has been the introduction of athermal lasers based on laser-diode pumping of Nd:YAG and products are now emerging for use on the battlefield. The technical performance, efficiency, size, weight and power for these lasers, has been key to driving the new production designs. In this paper, we review the development of the laser designs and their introduction since the advent of laser designation. In particular, we compare the relative performance and characteristics over the evolution of fielded laser designators. Moreover, we will review the key building blocks for the design of athermal lasers and describe some critical design issues for engineering and productionisation of a military laser system, including removal of thermal lensing, novel diode-pumping schemes and robustness over the environment. These will be exemplified using results from the development of the SELEX Galileo Type 163 Laser Target Designators. These will cover not only technical performance, power and efficiency, but also thermal management, mass, volume, cost and overall complexity for manufacture.
Novel Biomarker Discovery for Diagnostic and Therapeutic Strategies in Prostate Cancer
2014-03-01
aptamers that distinguish between prostate cancers that are likely to remain organ-confined and those with potential to metastasize, The scope of this...pilot is to generate DNA aptamers that selectively react with a prostate cancer cell line that remains confined to the prostate (LNCaP) vs. a...subpopulation of this cell line that has acquired the ability to metastasize aggressively, employing Cell-Selex and Aptamer -Facilitated Biomarker Discovery
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.
Advances in SELEX ES infrared detectors for space and astronomy
NASA Astrophysics Data System (ADS)
Knowles, P.; Hipwood, L.; Baker, I.; Weller, H.
2017-11-01
Selex ES produces a wide range of infrared detectors from mercury cadmium telluride (MCT) and triglycine sulfate (TGS), and has supplied both materials into space programmes spanning a period of over 40 years. Current development activities that underpin potential future space missions include large format arrays for near- and short-wave infrared (NIR and SWIR) incorporating radiation-hard designs and suppression of glow. Improved heterostructures are aimed at the reduction of dark currents and avalanche photodiodes (APDs), and parallel studies have been undertaken for low-stress MCT array mounts. Much of this development work has been supported by ESA, UK Space, and ESO, and some has been performed in collaboration with the UK Astronomy Technology Centre and E2V. This paper focuses on MCT heterostructure developments and novel design elements in silicon read-out chips (ROICs). The 2048 x 2048 element, 17um pitch ROIC for ESA's SWIR array development forms the basis for the largest cooled infrared detector manufactured in Europe. Selex ES MCT is grown by metal organic vapour phase epitaxy (MOVPE), currently on 75mm diameter GaAs substrates. The MCT die size of the SWIR array is 35mm square and only a single array can be printed on the 75mm diameter wafer, utilising only 28% of the wafer area. The situation for 100mm substrates is little better, allowing only 2 arrays and 31% utilisation. However, low cost GaAs substrates are readily available in 150mm diameter and the MCT growth is scalable to this size, offering the real possibility of 6 arrays per wafer with 42% utilisation. A similar 2k x 2k ROIC is the goal of ESA's NIR programme, which is currently in phase 2 with a 1k x 1k demonstrator, and a smaller 320 x 256 ROIC (SAPHIRA) has been designed for ESO for the adaptive optics application in the VLT Gravity instrument. All 3 chips have low noise source-follower architecture and are enabled for MCT APD arrays, which have been demonstrated by ESO to be capable of single photon detection. The possibility therefore exists in the near future of demonstrating a photon counting, 2k x 2k SWIR MCT detector manufactured on an affordable wafer scale of 6 arrays per wafer.
Pang, Ka Ming; Castanotto, Daniela; Li, Haitang; Scherer, Lisa; Rossi, John J
2018-01-09
Gene therapy by engineering patient's own blood cells to confer HIV resistance can potentially lead to a functional cure for AIDS. Toward this goal, we have previously developed an anti-HIV lentivirus vector that deploys a combination of shRNA, ribozyme and RNA decoy. To further improve this therapeutic vector against viral escape, we sought an additional reagent to target HIV integrase. Here, we report the development of a new strategy for selection and expression of aptamer for gene therapy. We developed a SELEX protocol (multi-tag SELEX) for selecting RNA aptamers against proteins with low solubility or stability, such as integrase. More importantly, we expressed these aptamers in vivo by incorporating them in the terminal loop of shRNAs. This novel strategy allowed efficient expression of the shRNA-aptamer fusions that targeted RNAs and proteins simultaneously. Expressed shRNA-aptamer fusions targeting HIV integrase or reverse transcriptase inhibited HIV replication in cell cultures. Viral inhibition was further enhanced by combining an anti-integrase aptamer with an anti-HIV Tat-Rev shRNA. This construct exhibited efficacy comparable to that of integrase inhibitor Raltegravir. Our strategy for the selection and expression of RNA aptamers can potentially extend to other gene therapy applications. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
Field testing of a next generation pointer/tracker for IRCM
NASA Astrophysics Data System (ADS)
Chapman, Stuart; Wildgoose, Iain; McDonald, Eric; Duncan, Stuart
2008-10-01
SELEX Galileo has been involved in the development, manufacture and support of high performance electro-optic pointing and stabilisation systems for over forty years. The Company currently supplies the pointer/trackers for the AN/AAQ-24(V) NEMESIS DIRCM system, for which over 1,000 combat-proven units have been produced and deployed in the US, the UK and other nations. In 2007, SELEX Galileo embarked on an internally funded programme to develop ECLIPSE, a new advanced, lightweight, low-cost IRCM pointer/tracker, exploiting the extensive knowledge and experience gained from previous targeting and IRCM programmes. The ECLIPSE design is centred on a low inertia, two-axis servo mechanism with a strap-down inertial sensor and advanced sightline control algorithms, allowing effective tracking through the nadir and providing superior sightline performance. The programme involved the production of three demonstrator units in 2007, and two pre-production units in 2008. The demonstrator units were first trialled as part of a NEMESIS DIRCM system in late 2007, and in April 2008 100% success was achieved in jamming live-fire demonstrations. Helicopter installation and ground testing of a UK only trials system is complete, initial flight testing has just begun, and the airborne test and evaluation scheduled for late summer 2008 will bring the ECLIPSE System to technology readiness to level 7 (TRL7). This paper describes the Eclipse performance demonstrated to date.
Brozovic, Matija; Dantec, Christelle; Dardaillon, Justine; Dauga, Delphine; Faure, Emmanuel; Gineste, Mathieu; Louis, Alexandra; Naville, Magali; Nitta, Kazuhiro R; Piette, Jacques; Reeves, Wendy; Scornavacca, Céline; Simion, Paul; Vincentelli, Renaud; Bellec, Maelle; Aicha, Sameh Ben; Fagotto, Marie; Guéroult-Bellone, Marion; Haeussler, Maximilian; Jacox, Edwin; Lowe, Elijah K; Mendez, Mickael; Roberge, Alexis; Stolfi, Alberto; Yokomori, Rui; Brown, C Titus; Cambillau, Christian; Christiaen, Lionel; Delsuc, Frédéric; Douzery, Emmanuel; Dumollard, Rémi; Kusakabe, Takehiro; Nakai, Kenta; Nishida, Hiroki; Satou, Yutaka; Swalla, Billie; Veeman, Michael; Volff, Jean-Nicolas; Lemaire, Patrick
2018-01-04
ANISEED (www.aniseed.cnrs.fr) is the main model organism database for tunicates, the sister-group of vertebrates. This release gives access to annotated genomes, gene expression patterns, and anatomical descriptions for nine ascidian species. It provides increased integration with external molecular and taxonomy databases, better support for epigenomics datasets, in particular RNA-seq, ChIP-seq and SELEX-seq, and features novel interactive interfaces for existing and novel datatypes. In particular, the cross-species navigation and comparison is enhanced through a novel taxonomy section describing each represented species and through the implementation of interactive phylogenetic gene trees for 60% of tunicate genes. The gene expression section displays the results of RNA-seq experiments for the three major model species of solitary ascidians. Gene expression is controlled by the binding of transcription factors to cis-regulatory sequences. A high-resolution description of the DNA-binding specificity for 131 Ciona robusta (formerly C. intestinalis type A) transcription factors by SELEX-seq is provided and used to map candidate binding sites across the Ciona robusta and Phallusia mammillata genomes. Finally, use of a WashU Epigenome browser enhances genome navigation, while a Genomicus server was set up to explore microsynteny relationships within tunicates and with vertebrates, Amphioxus, echinoderms and hemichordates. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
Ishihama, Akira; Kori, Ayako; Koshio, Etsuko; Yamada, Kayoko; Maeda, Hiroto; Shimada, Tomohiro; Makinoshima, Hideki; Iwata, Akira; Fujita, Nobuyuki
2014-08-01
The expression pattern of the Escherichia coli genome is controlled in part by regulating the utilization of a limited number of RNA polymerases among a total of its approximately 4,600 genes. The distribution pattern of RNA polymerase changes from modulation of two types of protein-protein interactions: the interaction of core RNA polymerase with seven species of the sigma subunit for differential promoter recognition and the interaction of RNA polymerase holoenzyme with about 300 different species of transcription factors (TFs) with regulatory functions. We have been involved in the systematic search for the target promoters recognized by each sigma factor and each TF using the newly developed Genomic SELEX system. In parallel, we developed the promoter-specific (PS)-TF screening system for identification of the whole set of TFs involved in regulation of each promoter. Understanding the regulation of genome transcription also requires knowing the intracellular concentrations of the sigma subunits and TFs under various growth conditions. This report describes the intracellular levels of 65 species of TF with known function in E. coli K-12 W3110 at various phases of cell growth and at various temperatures. The list of intracellular concentrations of the sigma factors and TFs provides a community resource for understanding the transcription regulation of E. coli under various stressful conditions in nature. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Kong, Hoon Young; Byun, Jonghoe
2015-01-01
Prostatic acid phosphatase (PAP) expression increases proportionally with prostate cancer progression, making it useful in prognosticating intermediate to high-risk prostate cancers. A novel ligand that can specifically bind to PAP would be very helpful for guiding prostate cancer therapy. RNA aptamers bind to target molecules with high specificity and have key advantages such as low immunogenicity and easy synthesis. Here, human PAP-specific aptamers were screened from a 2′-fluoropyrimidine (FY)-modified RNA library by SELEX. The candidate aptamer families were identified within six rounds followed by analysis of their sequences and PAP-specific binding. A gel shift assay was used to identify PAP binding aptamers and the 6N aptamer specifically bound to PAP with a Kd value of 118 nM. RT-PCR and fluorescence labeling analyses revealed that the 6N aptamer bound to PAP-positive mammalian cells, such as PC-3 and LNCaP. IMR-90 negative control cells did not bind the 6N aptamer. Systematic minimization analyses revealed that 50 nucleotide sequences and their two hairpin structures in the 6N 2′-FY RNA aptamer were equally important for PAP binding. Renewed interest in PAP combined with the versatility of RNA aptamers, including conjugation of anti-cancer drugs and nano-imaging probes, could open up a new route for early theragnosis of prostate cancer. PMID:25591398
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…
Infrared detectors for Earth observation
NASA Astrophysics Data System (ADS)
Barnes, K.; Davis, R. P.; Knowles, P.; Shorrocks, N.
2016-05-01
IASI (Infrared Atmospheric Sounding Interferometer), developed by CNES and launched since 2006 on the Metop satellites, is established as a major source of data for atmospheric science and weather prediction. The next generation - IASI NG - is a French national contribution to the Eumetsat Polar System Second Generation on board of the Metop second generation satellites and is under development by Airbus Defence and Space for CNES. The mission aim is to achieve twice the performance of the original IASI instrument in terms of sensitivity and spectral resolution. In turn, this places very demanding requirements on the infrared detectors for the new instrument. Selex ES in Southampton has been selected for the development of the infrared detector set for the IASI-NG instruments. The wide spectral range, 3.6 to 15.5 microns, is covered in four bands, each served by a dedicated detector design, with a common 4 x 4 array format of 1.3 mm square macropixels. Three of the bands up to 8.7 microns employ photovoltaic MCT (mercury cadmium telluride) technology and the very long wave band employs photoconductive MCT, in common with the approach taken between Airbus and Selex ES for the SEVIRI instrument on Second Generation Meteosat. For the photovoltaic detectors, the MCT crystal growth of heterojunction photodiodes is by the MOVPE technique (metal organic vapour phase epitaxy). Novel approaches have been taken to hardening the photovoltaic macropixels against localised crystal defects, and integrating transimpedance amplifiers for each macropixel into a full-custom silicon read out chip, which incorporates radiation hard design.
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.
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…
Laser manufacturing: strategies for dealing with the challenges
NASA Astrophysics Data System (ADS)
Barr, John R. M.
2012-09-01
Laser manufacturing in Edinburgh was initiated in 1963 by Ferranti (one of the previous names for SELEX Galileo). Since 2003 a modernized range of military lasers has been established. Innovation, both technical and in other aspects of the business, has enabled the design and manufacture of world leading laser designators and countermeasure lasers. Specific examples will be given including: the application of Geometric Algebra to resonator design; novel alignment free optical parametric oscillators; techniques for designing thermally insensitive laser diode pump heads; and methods for contamination control in lasers.
Main Port Mechanism for PRISMA
NASA Astrophysics Data System (ADS)
Caprini, G. C.; Ceccherini, M.; Brotini, M.; Bini, A.; Corsini, R.; Gasparini, L.; Battazza, F.; Formaro, R.
2013-09-01
A high complexity Main Port Mechanism (MPM) has been designed and produced by Selex ES in co- operation with HighFTech Engineering, an Italian PMI, in the frame of PRISMA (PRecursore IperSpettrale della Missione Applicativa) instrument.The Main Port Mechanism is located at the entrance of the Optical Head having the function of opening and closing a door.The paper describes the requirements drived the conceptual design, the detailed design and the qualification tests performed on the mechanism. A description of the foreseen test flow and set-up is also given.
NASA Astrophysics Data System (ADS)
Rossi, Alessandro; Acito, Nicola; Diani, Marco; Corsini, Giovanni; De Ceglie, Sergio Ugo; Riccobono, Aldo; Chiarantini, Leandro
2014-10-01
Airborne hyperspectral imagery is valuable for military and civilian applications, such as target identification, detection of anomalies and changes within multiple acquisitions. In target detection (TD) applications, the performance assessment of different algorithms is an important and critical issue. In this context, the small number of public available hyperspectral data motivated us to perform an extensive measurement campaign including various operating scenarios. The campaign was organized by CISAM in cooperation with University of Pisa, Selex ES and CSSN-ITE, and it was conducted in Viareggio, Italy in May, 2013. The Selex ES airborne hyperspectral sensor SIM.GA was mounted on board of an airplane to collect images over different sites in the morning and afternoon of two subsequent days. This paper describes the hyperspectral data collection of the trial. Four different sites were set up, representing a complex urban scenario, two parking lots and a rural area. Targets with dimensions comparable to the sensor ground resolution were deployed in the sites to reproduce different operating situations. An extensive ground truth documentation completes the data collection. Experiments to test anomalous change detection techniques were set up changing the position of the deployed targets. Search and rescue scenarios were simulated to evaluate the performance of anomaly detection algorithms. Moreover, the reflectance signatures of the targets were measured on the ground to perform spectral matching in varying atmospheric and illumination conditions. The paper presents some preliminary results that show the effectiveness of hyperspectral data exploitation for the object detection tasks of interest in this work.
Further developments of 8μm pitch MCT pixels at Finmeccanica (formerly Selex ES)
NASA Astrophysics Data System (ADS)
Jeckells, David; McEwen, R. Kennedy; Bains, Sudesh; Herbert, Martin
2016-05-01
Finmeccanica (formerly Selex ES) introduced high performance mercury cadmium telluride (MCT) infrared detectors on an 8μm pitch in 2015 with their SuperHawk device which builds on standard production processes already used for the manufacture of 24μm, 20μm, 16μm and 12μm pitch devices. The flexibility of the proprietary Finmeccanica designed diode structure, used in conjunction with the mature production Metal Organic Vapour Phase Epitaxy (MOVPE) MCT growth process at Finmeccanica, enables fine control of diode electrical and optical structure including free choice of cut-off wavelength. The mesa pixel design inherently provides major system performance benefits by reducing blurring mechanisms, including optical scattering, inter-pixel cross-talk and carrier diffusion, to negligible levels. The SuperHawk detector has demonstrated unrivalled MTF and NETD performance, even when operating at temperatures in excess of 120K. The SuperHawk Integrated Detector Cooler Assembly (IDCA) benefits from recent dewar developments at Finmeccanica, which have improved thermal efficiencies while maintaining mechanical integrity over a wide range of applications, enabling use of smaller cryo-coolers to reduce system SWAP-C. Performance and qualification results are presented together with example imagery. SuperHawk provides an easy high resolution upgrade for systems currently based on standard definition 16μm and 15μm infrared detector formats. The paper also addresses further work to increase the operating temperature of the established 8μm process, exploiting High Operating Temperature (HOT) MCT at Finmeccanica, as well as options for LWIR variants of the SuperHawk device.
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.
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.
Kim, Jin Sun; Park, Su Jung; Kwak, Kyung Jin; Kim, Yeon Ok; Kim, Joo Yeol; Song, Jinkyung; Jang, Boseung; Jung, Che-Hun; Kang, Hunseung
2007-01-01
Despite the fact that cold shock domain proteins (CSDPs) and glycine-rich RNA-binding proteins (GRPs) have been implicated to play a role during the cold adaptation process, their importance and function in eukaryotes, including plants, are largely unknown. To understand the functional role of plant CSDPs and GRPs in the cold response, two CSDPs (CSDP1 and CSDP2) and three GRPs (GRP2, GRP4 and GRP7) from Arabidopsis thaliana were investigated. Heterologous expression of CSDP1 or GRP7 complemented the cold sensitivity of BX04 mutant Escherichia coli that lack four cold shock proteins (CSPs) and is highly sensitive to cold stress, and resulted in better survival rate than control cells during incubation at low temperature. In contrast, CSDP2 and GRP4 had very little ability. Selective evolution of ligand by exponential enrichment (SELEX) revealed that GRP7 does not recognize specific RNAs but binds preferentially to G-rich RNA sequences. CSDP1 and GRP7 had DNA melting activity, and enhanced RNase activity. In contrast, CSDP2 and GRP4 had no DNA melting activity and did not enhance RNAase activity. Together, these results indicate that CSDPs and GRPs help E.coli grow and survive better during cold shock, and strongly imply that CSDP1 and GRP7 exhibit RNA chaperone activity during the cold adaptation process. PMID:17169986
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...
A Study of Multiplicities in Hadronic Interactions (in Spanish)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Estrada Tristan, Nora Patricia; /San Luis Potosi U.
Using data from the SELEX (Fermilab E781) experiment obtained with a minimum-bias trigger, we study multiplicity and angular distributions of secondary particles produced in interactions in the experimental targets. We observe interactions of {Sigma}{sup -}, proton, {pi}{sup -}, and {pi}{sup +}, at beam momenta between 250 GeV/c and 650 GeV/c, in copper, polyethylene, graphite, and beryllium targets. We show that the multiplicity and angular distributions for meson and baryon beams at the same momentum are identical. We also show that the mean multiplicity increases with beam momentum, and presents only small variations with the target material.
Hedayati Ch, Mojtaba; Amani, Jafar; Sedighian, Hamid; Amin, Mohsen; Salimian, Jafar; Halabian, Raheleh; Imani Fooladi, Abbas Ali
2016-09-01
Staphylococcus aureus are potent human pathogens possessing arsenal of virulence factors. Staphylococcal food poisoning (SFP) and respiratory infections mediated by staphylococcal enterotoxin B (SEB) are common clinical manifestations. Many diagnostic techniques are based on serological detection and quantification of SEB in different food and clinical samples. Aptamers are known as new therapeutic and detection tools which are available in different ssDNA, dsDNA and protein structures. In this study, we used a new set of ssDNA aptamers against SEB. The methods used included preparation of a dsDNA library using standard SEB protein as the target analyte, affinity chromatography matrix in microfuge tubes, SELEX procedures to isolate specific ssDNA-aptamer as an affinity ligand, aptamer purification using ethanol precipitation method, affinity binding assay using ELISA, aptamer cloning and specificity test. Among 12 readable sequences, three of them were selected as the most appropriate aptamer because of their affinity and specificity to SEB. This study presents a new set of ssDNA aptamer with favorable selectivity to SEB through 12 rounds of SELEX. Selected aptamers were used to detect SEB in infected serum samples. Results showed that SEB c1 aptamer (2 µg SEB/100 nM aptamer) had favorable specificity to SEB (kd = 2.3 × 10(-11) ). In conclusion, aptamers can be considered as useful tools for detecting and evaluating SEB. The results showed that affinity chromatography was an affordable assay with acceptable accuracy to isolate sensitive and selective novel aptamers. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Charge Gain, Voltage Gain, and Node Capacitance of the SAPHIRA Detector Pixel by Pixel
NASA Astrophysics Data System (ADS)
Pastrana, Izabella M.; Hall, Donald N. B.; Baker, Ian M.; Jacobson, Shane M.; Goebel, Sean B.
2018-01-01
The University of Hawai`i Institute for Astronomy has partnered with Leonardo (formerly Selex) in the development of HgCdTe linear mode avalanche photodiode (L-APD) SAPHIRA detectors. The SAPHIRA (Selex Avalanche Photodiode High-speed Infra-Red Array) is ideally suited for photon-starved astronomical observations, particularly near infrared (NIR) adaptive optics (AO) wave-front sensing. I have measured the stability, and linearity with current, of a 1.7-um (10% spectral bandpass) infrared light emitting diode (IR LED) used to illuminate the SAPHIRA and have then utilized this source to determine the charge gain (in e-/ADU), voltage gain (in uV/ADU), and node capacitance (in fF) for each pixel of the 320x256@24um SAPHIRA. These have previously only been averages over some sub-array. Determined from the ratio of the temporal averaged signal level to variance under constant 1.7-um LED illumination, I present the charge gain pixel-by-pixel in a 64x64 sub-array at the center of the active area of the SAPHIRA (analyzed separately as four 32x32 sub-arrays) to be about 1.6 e-/ADU (σ=0.5 e-/ADU). Additionally, the standard technique of varying the pixel reset voltage (PRV) in 10 mV increments and recording output frames for the same 64x64 subarray found the voltage gain per pixel to be about 11.7 uV/ADU (σ=0.2 uV/ADU). Finally, node capacitance was found to be approximately 23 fF (σ=6 fF) utilizing the aforementioned charge and voltage gain measurements. I further discuss the linearity measurements of the 1.7-um LED used in the charge gain characterization procedure.
Isolation and characterization of an RNA aptamer for the HPV-16 E7 oncoprotein.
Toscano-Garibay, Julia D; Benítez-Hess, María L; Alvarez-Salas, Luis M
2011-02-01
Cervical cancer is a common neoplastic disease affecting women worldwide. Expression of human papillomavirus type 16 (HPV-16) E6/E7 genes is frequently associated with cervical cancer, representing ideal targets for diagnostic and therapeutic strategies. Aptamers are oligonucleotide ligands capable of binding with high affinity and specificity to relevant markers in therapeutics and disease detection. The aim of the study was to isolate an RNA aptamer specific for the HPV-16 E7 protein. Aptamers were selected from a randomized oligonucleotide library using a modified SELEX method and recombinant HPV-16 E7 protein. Isolated aptamers were cloned and sequenced for in silico analysis. Interaction and electromobility shift assays (EMSA) were performed to establish aptamer specificity and affinity for E7. RNase footprinting and serial deletions of the aptamer and the E7 protein were made to characterize the aptamer-protein complex. Sandwich slot-blot assays were used for K(D) determination. After several rounds of SELEX, an aptamer (G5α3N.4) exhibited specificity for E7 using cell-free and protein extracts. G5α3N.4 binding yielded a K(D) comparable to aptamers directed to other small targets. Enzymatic and genetic analysis of G5α3N.4 binding showed a secondary structure with two stem-loop domains joined by single-stranded region contacting E7 in a clamp-like manner. The G5α3N.4 aptamer also produced specific complexes in HPV-positive cervical carcinoma cells. The affinity and specificity of G5α3N.4 binding domains for the HPV-16 E7 protein may be used for the detection of papillomavirus infection and cervical cancer. Copyright © 2011 IMSS. Published by Elsevier Inc. All rights reserved.
Thiel, William H.; Bair, Thomas; Peek, Andrew S.; Liu, Xiuying; Dassie, Justin; Stockdale, Katie R.; Behlke, Mark A.; Miller, Francis J.; Giangrande, Paloma H.
2012-01-01
Background The broad applicability of RNA aptamers as cell-specific delivery tools for therapeutic reagents depends on the ability to identify aptamer sequences that selectively access the cytoplasm of distinct cell types. Towards this end, we have developed a novel approach that combines a cell-based selection method (cell-internalization SELEX) with high-throughput sequencing (HTS) and bioinformatics analyses to rapidly identify cell-specific, internalization-competent RNA aptamers. Methodology/Principal Findings We demonstrate the utility of this approach by enriching for RNA aptamers capable of selective internalization into vascular smooth muscle cells (VSMCs). Several rounds of positive (VSMCs) and negative (endothelial cells; ECs) selection were performed to enrich for aptamer sequences that preferentially internalize into VSMCs. To identify candidate RNA aptamer sequences, HTS data from each round of selection were analyzed using bioinformatics methods: (1) metrics of selection enrichment; and (2) pairwise comparisons of sequence and structural similarity, termed edit and tree distance, respectively. Correlation analyses of experimentally validated aptamers or rounds revealed that the best cell-specific, internalizing aptamers are enriched as a result of the negative selection step performed against ECs. Conclusions and Significance We describe a novel approach that combines cell-internalization SELEX with HTS and bioinformatics analysis to identify cell-specific, cell-internalizing RNA aptamers. Our data highlight the importance of performing a pre-clear step against a non-target cell in order to select for cell-specific aptamers. We expect the extended use of this approach to enable the identification of aptamers to a multitude of different cell types, thereby facilitating the broad development of targeted cell therapies. PMID:22962591
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
SASS: a bi-spectral panoramic IRST - results from measurement campaigns with the Italian Navy
NASA Astrophysics Data System (ADS)
de Ceglie, S. U.; Lo Moro, M.; Vita, R.; Neri, A.; Barani, G.; Cavallini, M.; Quaranta, C.; Colombi, G.
2010-04-01
Modern naval warfare asks for alerting system able to detect classical & asymmetric threats in support to radar in environment in which radar has reduced performance (on or near the sea surface). More, capability to offer high resolution images helps in ship identification, coastal & harbor surveillance as well as night navigation and rescue. All these tasks can be performed by an infrared search and track (IRST) system. This paper describes the IRST named Silent Acquisition and Surveillance System (SASS), developed for the Italian Navy and the tests jointly carried out by SELEX GALILEO and Italian Navy to characterize the system.
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…
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.
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.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Vazquez Jauregui, Eric
2008-08-01
We studied several Ξ c + decay modes, most of them with a hyperon in the final state, and determined their branching ratios. The data used in this analysis come from the fixed target experiment SELEX, a multi-stage spectrometer with high acceptance for forward interactions, that took data during 1996 and 1997 at Fermilab with 600 GeV=c (mainly Σ -, π -) and 540 GeV/c (mainly p) beams incident on copper and carbon targets. The thesis mainly details the first observation of two Cabibbo-suppressed decay modes, Ξ c + → Σ +π -π + and Ξ c + → Σmore » -π +π +. The branching ratios of the decays relative to the Cabibbo-favored Ξ c + → Σ -π +π + are measured to be: Γ(Ξ c + → Σ -π +π +)/Γ(Ξ c + → Ξ -π +π +) = 0.184 ± 0.086. Systematic studies have been performed in order to check the stability of the measurements varying all cuts used in the selection of events over a wide interval and we do not observe evidence of any trend, so the systematic error is negligible in the final results because the quadrature sum of the total error is not affected. The branching ratios for the same decay modes of the Λ c + are measured to check the methodology of the analysis. The branching ratio of the decay mode Λ c + → Σ +π -π + is measured relative to Λ c + → pK - π +, while the one of the decay mode Λ c + → Σ -π +π +is relative to Λ c +→ Σ +π -π +, as they have been reported earlier. The results for the control modes are: Γ(Λ c +→ Σ +π -π +)/Γ(Λ c + → pK - π +) = 0.716 ± 0.144 and Γ(Λ c +→ Σ -π +π +)/Γ(Λ c + → Σ +π -π +) = 0.382 ± 0.104. The branching ratio of the decay mode Ξ c + → pK - π + relative to Ξ c + → Ξ -π +π + is considered as another control mode, the measured value is Γ(Ξ c + → pK -π +)/Γ(Ξ c + → Ξ -π +π +) = 0.194 ± 0.054. Systematic studies have been also performed for the control modes and all systematic variations are also small compared to the statistical error. We also report the first observation of two more decay modes, the Cabibbo-suppressed decay Ξ c + → Σ - K +π + and the doubly Cabibbo-suppressed decay Ξ c + → Σ +K +π -, but their branching ratios have not been measured up to now.« less
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.
Aptamers against pathogenic microorganisms
Davydova, Anna; Vorobjeva, Maria; Pyshnyi, Dmitrii; Altman, Sidney; Vlassov, Valentin; Venyaminova, Alya
2016-01-01
Abstract An important current issue of modern molecular medicine and biotechnology is the search for new approaches to early diagnostic assays and adequate therapy of infectious diseases. One of the promising solutions to this problem might be a development of nucleic acid aptamers capable of interacting specifically with bacteria, protozoa, and viruses. Such aptamers can be used for the specific recognition of infectious agents as well as for blocking of their functions. The present review summarizes various modern SELEX techniques used in this field, and of several currently identified aptamers against viral particles and unicellular organisms, and their applications. The prospects of applying nucleic acid aptamers for the development of novel detection systems and antibacterial and antiviral drugs are discussed. PMID:26258445
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.
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.
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.
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
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
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…
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
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.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Krishnamurthy, Malathy; Hennelly, Scott Patrick; Dale, Taraka T.
The most straightforward approach to altering the flux through a particular metabolic step is to increase or decrease the concentration of the enzyme catalyst. Until recently engineering strategies for altering gene expression have focused on transcription control using strong inducible promoters or by using one of several strategies to knock down or knock out a wasteful gene. Recently, synthetic riboregulators have been developed for translational regulation of gene expression. We report a new modular synthetic riboregulator class that has the potential to finely tune protein expression and independently control the concentration of each enzyme in an engineered metabolic pathway. Ourmore » design includes a cis-repressor at the 5’ end of the mRNA that forms a stem-loop helix occluding the ribosome binding site and blocking translation. An activating-RNA, expressed in trans, frees the RBS turning on translation. The overall architecture of the riboregulators is designed using Watson-Crick base-pairing stability followed by directed evolution on a portion of each trans-activator to fine tune translation. We report a cis-repressor that can completely shut off translation of antibiotic resistance reporters and a trans-activator that restores translation. We have shown it is possible to use riboregulators to achieve translational control of gene expression over a wide dynamic range. Using a bioluminescent reporter system, we demonstrated an ON/OFF ratio >300. We have demonstrated that a targeting sequence can be changed to develop riboregulators that can independently regulate translation of many genes with minimal cross-talk. In a SELEX experiment, we demonstrated that by subtly altering the sequence of the trans-activator, it is possible to alter the equilibrium between repressed and activated states and achieve intermediate translational control.« less
Tunable riboregulator switches for post-transcriptional control of gene expression
Krishnamurthy, Malathy; Hennelly, Scott Patrick; Dale, Taraka T.; ...
2015-07-13
The most straightforward approach to altering the flux through a particular metabolic step is to increase or decrease the concentration of the enzyme catalyst. Until recently engineering strategies for altering gene expression have focused on transcription control using strong inducible promoters or by using one of several strategies to knock down or knock out a wasteful gene. Recently, synthetic riboregulators have been developed for translational regulation of gene expression. We report a new modular synthetic riboregulator class that has the potential to finely tune protein expression and independently control the concentration of each enzyme in an engineered metabolic pathway. Ourmore » design includes a cis-repressor at the 5’ end of the mRNA that forms a stem-loop helix occluding the ribosome binding site and blocking translation. An activating-RNA, expressed in trans, frees the RBS turning on translation. The overall architecture of the riboregulators is designed using Watson-Crick base-pairing stability followed by directed evolution on a portion of each trans-activator to fine tune translation. We report a cis-repressor that can completely shut off translation of antibiotic resistance reporters and a trans-activator that restores translation. We have shown it is possible to use riboregulators to achieve translational control of gene expression over a wide dynamic range. Using a bioluminescent reporter system, we demonstrated an ON/OFF ratio >300. We have demonstrated that a targeting sequence can be changed to develop riboregulators that can independently regulate translation of many genes with minimal cross-talk. In a SELEX experiment, we demonstrated that by subtly altering the sequence of the trans-activator, it is possible to alter the equilibrium between repressed and activated states and achieve intermediate translational control.« less
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.
NASA Technical Reports Server (NTRS)
Cannone, Jaime J.; Barnes, Cindy L.; Achari, Aniruddha; Kundrot, Craig E.; Whitaker, Ann F. (Technical Monitor)
2001-01-01
The Sparse Matrix approach for obtaining lead crystallization conditions has proven to be very fruitful for the crystallization of proteins and nucleic acids. Here we report a Sparse Matrix developed specifically for the crystallization of protein-DNA complexes. This method is rapid and economical, typically requiring 2.5 mg of complex to test 48 conditions. The method was originally developed to crystallize basic fibroblast growth factor (bFGF) complexed with DNA sequences identified through in vitro selection, or SELEX, methods. Two DNA aptamers that bind with approximately nanomolar affinity and inhibit the angiogenic properties of bFGF were selected for co-crystallization. The Sparse Matrix produced lead crystallization conditions for both bFGF-DNA complexes.
Measurement of the Branching Ratio Lambda_c+ -> p pi+ pi- (in Spanish)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lopez-Hinojosa, Guillermo; /San Luis Potosi U.
2008-03-01
The confirmation of the Cabibbo-suppressed charm baryon decay mode {Lambda}{sub c}{sup +} {yields} p{pi}{sup +}{pi}{sup -} is reported. All data analyzed are from SELEX, a fixed target experiment at Fermilab that took data during 1996 and 1997, mainly with a 600 GeV/c {Sigma}{sup -} beam. The branching ratio of the Cabibbo-suppressed decay mode {Lambda}{sub c}{sup +} {yields} p{pi}{sup +}{pi}{sup -} relative to the Cabibbo-favored mode {Lambda}{sub c}{sup +} {yields} pK{sup -}{pi}{sup +} is measured to be: {Gamma}({Lambda}{sub c}{sup +} {yields} p{pi}{sup +}{pi}{sup -})/{Gamma}({Lambda}{sub c}{sup +} {yields} pK{sup -}{pi}{sup +}) = 0.103 {+-} 0.022.
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.
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.
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.
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.
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
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.
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.
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.
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
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
Recent BaBar Results on Hadron Spectroscopy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Robutti, E.; /INFN, Genoa
2005-08-29
Recent results from on hadronic spectroscopy are presented, based on data collected by the BaBar experiment between 1999 and 2004. The properties of the recently discovered D*{sub sJ}(2317){sup +} and D{sub sJ}(2460){sup +} states are studied: resonance parameters and ratios of decay rates are measured from continuum e{sup +}e{sup -} production, and production rates are measured from B decays. A search for the D*{sub sJ}(2632){sup +} state whose observation has been recently reported by the SELEX Collaboration, and a search for a charged partner of the charmonium-like X(3872) state, are performed, yielding negative results. Finally, extensive searches for several pentaquarkmore » candidates, both fully inclusive and in B decays, result in no positive evidence.« less
Aptamer Selection Express: A Novel Method for Rapid Single-Step Selection and Sensing of Aptamers
Fan, Maomian; McBurnett, Shelly Roper; Andrews, Carrie J.; Allman, Amity M.; Bruno, John G.; Kiel, Johnathan L.
2008-01-01
Here we describe a new DNA capture element (DCE) sensing system, based on the quenching and dequenching of a double-stranded aptamer. This system shows very good sensitivity and thermal stability. While quenching, dequenching, and separating the DCE systems made from different aptamers (all selected by SELEX), an alternative method to rapidly select aptamers was developed—the Aptamer Selection Express (ASExp). This process has been used to select aptamers against different types of targets (Bacillus anthracis spores, Bacillus thuringiensis spores, MS-2 bacteriophage, ovalbumin, and botulinum neurotoxin). The DCE systems made from botulinum neurotoxin aptamers selected by ASExp have been investigated. The results of this investigation indicate that ASExp can be used to rapidly select aptamers for the DCE sensing system. PMID:19183794
Avalanche photo diodes in the observatory environment: lucky imaging at 1-2.5 microns
NASA Astrophysics Data System (ADS)
Vaccarella, A.; Sharp, R.; Ellis, M.; Singh, S.; Bloxham, G.; Bouchez, A.; Conan, R.; Boz, R.; Bundy, D.; Davies, J.; Espeland, B.; Hart, J.; Herrald, N.; Ireland, M.; Jacoby, G.; Nielsen, J.; Vest, C.; Young, P.; Fordham, B.; Zovaro, A.
2016-08-01
The recent availability of large format near-infrared detectors with sub-election readout noise is revolutionizing our approach to wavefront sensing for adaptive optics. However, as with all near-infrared detector technologies, challenges exist in moving from the comfort of the laboratory test-bench into the harsh reality of the observatory environment. As part of the broader adaptive optics program for the GMT, we are developing a near-infrared Lucky Imaging camera for operational deployment at the ANU 2.3 m telescope at Siding Spring Observatory. The system provides an ideal test-bed for the rapidly evolving Selex/SAPHIRA eAPD technology while providing scientific imaging at angular resolution rivalling the Hubble Space Telescope at wavelengths λ = 1.3-2.5 μm.
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.
NASA Astrophysics Data System (ADS)
Sakaue, H.; Nishimura, T.; Fukuda, J.; Kato, T.
2017-12-01
In the Tokai region, central Japan, the long-term slow slip events (L-SSEs) observed on the subducting Philippine Sea Plate (PSP) from 2000 to 2005 and since 2013. Moreover, many short-term slow slip events (S-SSEs) have been observed in the Tokai region since 1996. Sakaue et al. (2017) reported that the spatiotemporal evolution of an L-SSE and S-SSEs on the PSP beneath the Tokai region from 2013 to 2015. This study is probably the first case that migration of slip for S-SSE (Mw < 6.0) was estimated solely using GNSS data in southwest Japan.We, here, extend our analysis period to be from 1994 to 2016. The GIPSY-OASIS II software was used to estimate daily coordinates of GNSS stations operated by GSI and JUNCO (the Japanese University Consortium for GPS Research) in the Tokai region. It is well known that GNSS time series have many systematic signals that do not result from SSEs. These systematic signals include, for example, seasonal variations, cosiesmic and post-seismic deformation of the 2004 off Southeast Kii Peninsula eqrthquake and the 2011 Tohoku-oki earthquake (Mw. 9.0), crustal deformation of volcanic activity on Miyake-jima island and so on. After removing these systematic signals, we applied a modified Network Inversion Filter (NIF) [Fukuda et al., 2008]. The original NIF [Segall & Matthews, 1997] assumes a constant hyperparameter for the temporal smoothing of slip rates and thus often results in oversmoothing of slip rates. The modified NIF assumes a time-variable hyperparameter, so that changes in slip rates are effectively extracted from GNSS time series.The results indicate that not only the spatiotemporal evolutions of the 2000 Tokai L-SSE and the 2013 L-SSE but also the spatiotemporal evolution of S-SSEs are estimated. We will present a comparison of the spatiotemporal evolutions between the 2000 Tokai L-SSE and the 2013 L-SSE and possible dependence of the occurrence style of S-SSEs on the occurrence of the L-SSEs.
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
Telescope Scientist on the Advanced X-ray Astrophysics Observatory
NASA Technical Reports Server (NTRS)
VanSpeybroeck, L.; Smith, Carl M. (Technical Monitor)
2002-01-01
This period included many scientific observations made with the Chandra Observatory. The results, as is well known, are spectacular. Fortunately, the High Resolution Mirror Assembly (HRMA) performance continues to be essentially identical to that predicted from ground calibration data. The Telescope Scientist Team has improved the mirror model to provide a more accurate description to the Chandra observers and enable them to reduce the systematic errors and uncertainties in their data reduction. We also have made considerable progress in improving the scattering model. There also has been progress in the scientific program. At this time 58 distant clusters of galaxies have been observed. We are performing a systematic analysis of this rather large data set for the purpose of determining absolute distances utilizing the Sunyaev Zel'dovich effect. These observations also have been used to study the evolution of the cluster baryon mass function and the cosmological constraints which result from this evolution.
Systematic study of magnetar outbursts
NASA Astrophysics Data System (ADS)
Coti Zelati, F.; Rea, N.; Pons, J. A.; Campana, S.; Esposito, P.
2017-12-01
We present the results of the systematic study of all magnetar outbursts observed to date through a reanalysis of data acquired in about 1100 X-ray observations. We track the temporal evolution of the luminosity for all these events, model empirically their decays, and estimate the characteristic decay time-scales and the energy involved. We study the link between different parameters (maximum luminosity increase, outburst peak luminosities, quiescent X-ray and bolometric luminosities, energetics, decay time-scales, magnetic field, spin-down luminosity and age), and reveal several correlations between different quantities. We discuss our results in the framework of the models proposed to explain the triggering mechanism and evolution of magnetar outbursts. The study is complemented by the Magnetar Outburst Online Catalog (http://www.magnetars.ice.csic.es), an interactive database where the user can plot any combination of the parameters derived in this work and download all reduced data.
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. PMID:25369195
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.
NASA Astrophysics Data System (ADS)
Chen, Y. F.; Chang, C. C.; Lee, C. Y.; Tung, J. C.; Liang, H. C.; Huang, K. F.
2018-01-01
Theoretical wave functions are analytically derived to characterize the propagation evolution of the Hermite-Gaussian (HG) beams transformed by a single-lens astigmatic mode converter with arbitrary angle. The derived wave functions are related to the combination of the rotation transform and the antisymmetric fractional Fourier transform. The derived formula is systematically validated by using an off-axis diode-pumped solid-state laser to generate various high-order HG beams for mode conversions. In addition to validation, the creation and evolution of vortex structures in the transformed HG beams are numerically manifested. The present theoretical analyses can be used not only to characterize the evolution of the transformed beams but to design the optical vortex beams with various forms.
Giada improved calibration of measurement subsystems
NASA Astrophysics Data System (ADS)
Della Corte, V.; Rotundi, A.; Sordini, R.; Accolla, M.; Ferrari, M.; Ivanovski, S.; Lucarelli, F.; Mazzotta Epifani, E.; Palumbo, P.
2014-12-01
GIADA (Grain Impact Analyzer and Dust Accumulator) is an in-situ instrument devoted to measure the dynamical properties of the dust grains emitted by the comet. An Extended Calibration activity using the GIADA Flight Spare Model has been carried out taking into account the knowledge gained through the analyses of IDPs and cometary samples returned from comet 81P/Wild 2. GIADA consists of three measurement subsystems: Grain Detection System, an optical device measuring the optical cross-section for individual dust; Impact Sensor an aluminum plate connected to 5 piezo-sensors measuring the momentum of impacting single dust grains; Micro Balance System measuring the cumulative deposition in time of dust grains smaller than 10 μm. The results of the analyses on data acquired with the GIADA PFM and the comparison with calibration data acquired during the pre-launch campaign allowed us to improve GIADA performances and capabilities. We will report the results of the following main activities: a) definition of a correlation between the 2 GIADA Models (PFM housed in laboratory and In-Flight Model on-board ROSETTA); b) characterization of the sub-systems performances (signal elaboration, sensitivities, space environment effects); c) new calibration measurements and related curves by means of the PFM model using realistic cometary dust analogues. Acknowledgements: GIADA was built by a consortium led by the Univ. Napoli "Parthenope" & INAF-Oss. Astr. Capodimonte, IT, in collaboration with the Inst. de Astrofisica de Andalucia, ES, Selex-ES s.p.a. and SENER. GIADA is presently managed & operated by Ist. di Astrofisica e Planetologia Spaziali-INAF, IT. GIADA was funded and managed by the Agenzia Spaziale Italiana, IT, with a support of the Spanish Ministry of Education and Science MEC, ES. GIADA was developed from a University of Kent, UK, PI proposal; sci. & tech. contribution given by CISAS, IT, Lab. d'Astr. Spat., FR, and Institutions from UK, IT, FR, DE and USA. We thank the RSGS/ESAC, RMOC/ESOC & Rosetta Project/ESTEC for their outstanding work. Science support provided by NASA through the US Rosetta Project managed by JPL/California Institute of Technology. GIADA calibrated data will be available through the ESA's PSA web site (www.rssd.esa.int/index.php?project=PSA&page=index).
Monitoring Comet 67P/C-G Micrometer Dust Flux: GIADA onboard Rosetta.
NASA Astrophysics Data System (ADS)
Della Corte, Vincenzo; Rotundi, Alessandra; Ivanovski, Stavro; Accolla, Mario; Ferrari, Marco; Sordini, Roberto; Lucarelli, Francesca; Zakharov, Vladimir; Fulle, Marco; Mazzotta Epifani, Elena; López-Moreno, José J.; Rodríguez, Julio; Colangeli, Luigi; Palumbo, Pasquale; Bussoletti, Ezio; Crifo, Jean-Francois; Esposito, Francesca; Green, Simon F.; Grün, Eberhard; Lamy, Philippe L.
2015-04-01
(21)ESA-ESAC, Camino Bajo del Castillo, s/n., Urb. Villafranca del Castillo, 28692 Villanueva de la Cañada, Madrid, Spagna The MicroBalance System (MBS) is one of the three measurement subsystems of GIADA, the Grain Impact Analyzer and Dust Accumulator on board the Rosetta/ESA spacecraft (S/C). It consists of five Quartz Crystal Microbalances (QCMs) in roughly orthogonal directions providing the cumulative dust flux of grains smaller than 10 microns. The MBS is continuously monitoring comet 67P/CG since the beginning of May 2014. During the first 4 months of measurements, before the insertion of the S/C in the bound orbit phase, there were no evidences of dust accumulation on the QCMs. Starting from the beginning of October, three out of five QCMs measured an increase of the deposited dust. The measured fluxes show, as expected, a strong anisotropy. In particular, the dust flux appears to be much higher from the Sun direction with respect to the comet direction. Acknowledgment: GIADA was built by a consortum led by the Univ. Napoli "Parthenope" & INAF- Oss. Astr. Capodimonte, in collaboration with the Inst. de Astrofisica de Andalucia, Selex-ES, FI and SENER. GIADA is presently managed & operated by Ist. di Astrofisica e Planetologia Spaziali-INAF, IT. GIADA was funded and managed by the Agenzia Spaziale Italiana, IT, with the support of the Spanish Ministry of Education and Science MEC, ES. GIADA was developed from a PI proposal from the University of Kent; sci. & tech. contribution were provided by CISAS, IT, Lab. d'Astr. Spat., FR, and Institutions from UK, IT, FR, DE and USA. We thank the RSGS/ESAC, RMOC/ESOC & Rosetta Project/ESTEC for their out-standing work. Science support provided was by NASA through the US Rosetta Project managed by the Jet Propulsion Laboratory/ California Institute of Technology. GIADA calibrated data will be available through ESA's PSA web site (www.rssd.esa.int/index.php? project=PSA&page=in dex). We would like to thank Angioletta Coradini for her contribution as a GIADA Co-I.
Workshop on Molecular Evolution
NASA Technical Reports Server (NTRS)
Cummings, Michael P.
2004-01-01
Molecular evolution has become the nexus of many areas of biological research. It both brings together and enriches such areas as biochemistry, molecular biology, microbiology, population genetics, systematics, developmental biology, genomics, bioinformatics, in vitro evolution, and molecular ecology. The Workshop provides an important contribution to these fields in that it promotes interdisciplinary research and interaction, and thus provides a glue that sticks together disparate fields. Due to the wide range of fields addressed by the study of molecular evolution, it is difficult to offer a comprehensive course in a university setting. It is rare for a single institution to maintain expertise in all necessary areas. In contrast, the Workshop is uniquely able to provide necessary breadth and depth by utilizing a large number of faculty with appropriate expertise. Furthermore, the flexible nature of the Workshop allows for rapid adaptation to changes in the dynamic field of molecular evolution. For example, the 2003 Workshop included recently emergent research areas of molecular evolution of development and genomics.
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.
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.
Wang, Xue-Yong; Liao, Cai-Li; Liu, Si-Qi; Liu, Chun-Sheng; Shao, Ai-Juan; Huang, Lu-Qi
2013-05-01
This paper put forward a more accurate identification method for identification of Chinese materia medica (CMM), the systematic identification of Chinese materia medica (SICMM) , which might solve difficulties in CMM identification used the ordinary traditional ways. Concepts, mechanisms and methods of SICMM were systematically introduced and possibility was proved by experiments. The establishment of SICMM will solve problems in identification of Chinese materia medica not only in phenotypic characters like the mnorphous, microstructure, chemical constituents, but also further discovery evolution and classification of species, subspecies and population in medical plants. The establishment of SICMM will improve the development of identification of CMM and create a more extensive study space.
Song, Myeong-Sub; Sekhon, Simranjeet Singh; Shin, Woo-Ri; Rhee, Sung-Keun; Ko, Jung Ho; Kim, Sang Yong; Min, Jiho; Ahn, Ji-Young; Kim, Yang-Hoon
2018-05-01
Shigella sonnei isolate invasion plasmid antigen protein, IpaH, was successfully expressed in recombinant overexpression bacterial system. The soluble expression IpaH was enhanced with molecular chaperon co-expressed environment. Specific aptamer IpaH17 was isolated through the SELEX process and showed fM binding affinity. IpaH17-SPR biosensor platform was involved to verify the binding sensitivity and specificity. The IpaH concentration dependent IpaH17-SPR sensor response was highly linear with a linear regression constant of 99.4% in the range between 0 and 100 ng/mL. In addition, S. sonnei revealed the specific RU value and detected in a real-time manner within 1 hour. Our study indicated that IpaH17-SPR sensor can allow for rapid, sensitive and specific determination of Shigella sonnei virulent factor.
By-product formation in repetitive PCR amplification of DNA libraries during SELEX.
Tolle, Fabian; Wilke, Julian; Wengel, Jesper; Mayer, Günter
2014-01-01
The selection of nucleic acid aptamers is an increasingly important approach to generate specific ligands binding to virtually any molecule of choice. However, selection-inherent amplification procedures are prone to artificial by-product formation that prohibits the enrichment of target-recognizing aptamers. Little is known about the formation of such by-products when employing nucleic acid libraries as templates. We report on the formation of two different forms of by-products, named ladder- and non-ladder-type observed during repetitive amplification in the course of in vitro selection experiments. Based on sequence information and the amplification behaviour of defined enriched nucleic acid molecules we suppose a molecular mechanism through which these amplification by-products are built. Better understanding of these mechanisms might help to find solutions minimizing by-product formation and improving the success rate of aptamer selection.
Improvements to quality of needle coke by controlled carbonized conditions
NASA Astrophysics Data System (ADS)
Liu, Dong; Lou, Bin; Yu, Ran; Chen, Qingtai; Li, Zhiheng; Zhang, Yadong
2018-06-01
In this study, the selected aromatic-rich fraction derived from hydrocracking tail oil was carbonized and further improvement in the quality of resultant coke was achieved by promoting temperature at the solidification stage. In comparison with conventional process carried out isothermally and isobarically, the coupling analysis between formation and subsequent uni-axial orientation of mesophase textures during the controlled process was systematically discussed on the basis of the mutual relevance among mesophase texture evolution, gas evolution rate and solidification rate of intermediates. The results show that on the premise that formation of bulk mesophase, appropriate rate of gas evolution at a right time of solidification contributes to fine produces fine fibrous mesophase aligned uni-axially and less pores. Moreover, the intermediates with solidification index of 2˜6 are suitable for deformation induced by gas evolution.
Role of a Transcriptional Regulator in Programmed Cell Death and Plant Development
DOE Office of Scientific and Technical Information (OSTI.GOV)
Julie M. Stone
2008-09-13
The long-term goal of this research is to understand the role(s) and molecular mechanisms of programmed cell death (PCD) in the controlling plant growth, development and responses to biotic and abiotic stress. We developed a genetic selection scheme to identify A. thaliana FB1-resistant (fbr) mutants as a way to find genes involved in PCD (Stone et al., 2000; Stone et al., 2005; Khan and Stone, 2008). The disrupted gene in fbr6 (AtSPL14) responsible for the FB1-insensitivity and plant architecture phenotypes encodes a plant-specific SBP DNA-binding domain transcriptional regulator (Stone et al., 2005; Liang et al., 2008). This research plan ismore » designed to fill gaps in the knowledge about the role of SPL14 in plant growth and development. The work is being guided by three objectives aimed at determining the pathways in which SPL14 functions to modulate PCD and/or plant development: (1) determine how SPL14 functions in plant development, (2) identify target genes that are directly regulated by SPL14, and (3) identify SPL14 modifications and interacting proteins. We made significant progress during the funding period. Briefly, some major accomplishments are highlighted below: (1) To identify potential AtSPL14 target genes, we identified a consensus DNA binding site for the AtSPL14 SBP DNA-binding domain using systematic evolution of ligands by exponential selection (SELEX) and site-directed mutagenesis (Liang et al., 2008). This consensus binding site was used to analyze Affymetrix microarray gene expression data obtained from wild-type and fbr6 mutant plants to find possible AtSPL14-regulated genes. These candidate AtSPL14-regulated genes are providing new information on the molecular mechanisms linking plant PCD and plant development through modulation of the 26S proteasome. (2) Transgenic plants expressing epitope-tagged versions of AtSPL14 are being used to confirm the AtSPL14 targets (by ChIP-PCR) and further dissect the molecular interactions (Nazarenus, Liang and Stone, in preparation) (3) Double mutants generated between fbr6 and various accelerated cell death (acd) mutants indicate that sphingolipid metabolism is influenced by AtSPL14 and sphingolipidomics profiling supports this conclusion (Lin, Markham and Stone, in preparation). (4) A new set of phenotypes have been uncovered in the original fbr6-1 mutant, including a short-root phenotype related to auxin signaling and altered photosynthetic parameters related to stomatal density and conductance (Lin and Stone, in preparation; Lin, Madhavan and Stone, in preparation). Additional AtSPL14-related mutants and transgenic plants have been generated to effectively dissect the functions of AtSPL14, including a dominant negative fbr6-2 allele and transgenic plants overexpressing FBR6/AtSPL14 that display an accelerated cell death (acd) phenotype.« less
Concept Formation and Abstraction.
ERIC Educational Resources Information Center
Lunzer, Eric A.
1979-01-01
This paper examines the nature of concepts and conceptual processes and the manner of their formation. It argues that a process of successive abstraction and systematization is central to the evolution of conceptual structures. Classificatory processes are discussed and three levels of abstraction outlined. (Author/SJL)
Bridging Inter- and Intraspecific Trait Evolution with a Hierarchical Bayesian Approach.
Kostikova, Anna; Silvestro, Daniele; Pearman, Peter B; Salamin, Nicolas
2016-05-01
The evolution of organisms is crucially dependent on the evolution of intraspecific variation. Its interactions with selective agents in the biotic and abiotic environments underlie many processes, such as intraspecific competition, resource partitioning and, eventually, species formation. Nevertheless, comparative models of trait evolution neither allow explicit testing of hypotheses related to the evolution of intraspecific variation nor do they simultaneously estimate rates of trait evolution by accounting for both trait mean and variance. Here, we present a model of phenotypic trait evolution using a hierarchical Bayesian approach that simultaneously incorporates interspecific and intraspecific variation. We assume that species-specific trait means evolve under a simple Brownian motion process, whereas species-specific trait variances are modeled with Brownian or Ornstein-Uhlenbeck processes. After evaluating the power of the method through simulations, we examine whether life-history traits impact evolution of intraspecific variation in the Eriogonoideae (buckwheat family, Polygonaceae). Our model is readily extendible to more complex scenarios of the evolution of inter- and intraspecific variation and presents a step toward more comprehensive comparative models for macroevolutionary studies. © The Author(s) 2016. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Evans, Luke; Manley, Kate
2016-06-01
Single-incision laparoscopic surgery represents an evolution of minimally invasive techniques, but has been a controversial development. A cosmetic advantage is stated by many authors, but has not been found to be universally present or even of considerable importance by patients. This systematic review and meta-analysis demonstrates that there is a cosmetic advantage of the technique regardless of the operation type. The treatment effect in terms of cosmetic improvement is of the order of 0.63.
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
Monte Carlo generators for studies of the 3D structure of the nucleon
Avakian, Harut; D'Alesio, U.; Murgia, F.
2015-01-23
In this study, extraction of transverse momentum and space distributions of partons from measurements of spin and azimuthal asymmetries requires development of a self consistent analysis framework, accounting for evolution effects, and allowing control of systematic uncertainties due to variations of input parameters and models. Development of realistic Monte-Carlo generators, accounting for TMD evolution effects, spin-orbit and quark-gluon correlations will be crucial for future studies of quark-gluon dynamics in general and 3D structure of the nucleon in particular.
New nonlinear evolution equations from surface theory
NASA Astrophysics Data System (ADS)
Gürses, Metin; Nutku, Yavuz
1981-07-01
We point out that the connection between surfaces in three-dimensional flat space and the inverse scattering problem provides a systematic way for constructing new nonlinear evolution equations. In particular we study the imbedding for Guichard surfaces which gives rise to the Calapso-Guichard equations generalizing the sine-Gordon (SG) equation. Further, we investigate the geometry of surfaces and their imbedding which results in the Korteweg-deVries (KdV) equation. Then by constructing a family of applicable surfaces we obtain a generalization of the KdV equation to a compressible fluid.
Reconstructing human evolution: Achievements, challenges, and opportunities
Wood, Bernard
2010-01-01
This contribution reviews the evidence that has resolved the branching structure of the higher primate part of the tree of life and the substantial body of fossil evidence for human evolution. It considers some of the problems faced by those who try to interpret the taxonomy and systematics of the human fossil record. How do you to tell an early human taxon from one in a closely related clade? How do you determine the number of taxa represented in the human clade? How can homoplasy be recognized and factored into attempts to recover phylogeny? PMID:20445105
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
Systematics, diversity, genetics, and evolution of wild and cultivated potatoes
USDA-ARS?s Scientific Manuscript database
Cultivated potato, Solanum tuberosum L., is the third most important food crop and is grown and consumed worldwide. Indigenous primitive cultivated (landrace) potatoes, and wild potatoes, all classified as Solanum section Petota, are widely used for potato improvement. Members of section Petota are ...
Evolution of CMB spectral distortion anisotropies and tests of primordial non-Gaussianity
NASA Astrophysics Data System (ADS)
Chluba, Jens; Dimastrogiovanni, Emanuela; Amin, Mustafa A.; Kamionkowski, Marc
2017-04-01
Anisotropies in distortions to the frequency spectrum of the cosmic microwave background (CMB) can be created through spatially varying heating processes in the early Universe. For instance, the dissipation of small-scale acoustic modes does create distortion anisotropies, in particular for non-Gaussian primordial perturbations. In this work, we derive approximations that allow describing the associated distortion field. We provide a systematic formulation of the problem using Fourier-space window functions, clarifying and generalizing previous approximations. Our expressions highlight the fact that the amplitudes of the spectral-distortion fluctuations induced by non-Gaussianity depend also on the homogeneous value of those distortions. Absolute measurements are thus required to obtain model-independent distortion constraints on primordial non-Gaussianity. We also include a simple description for the evolution of distortions through photon diffusion, showing that these corrections can usually be neglected. Our formulation provides a systematic framework for computing higher order correlation functions of distortions with CMB temperature anisotropies and can be extended to describe correlations with polarization anisotropies.
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)
Rimbert, J. N.; Lafargue, C.; Pachot, M.; Dumas, F.; Eugene, M.; Brunelle, F.; Lallemand, D.
1990-07-01
Biochemical constitution of the hematoma is depending of its evolution. In order to obtain a reliable diagnostic of the NMR images in case of vascular accidents, a systematic study of the time-evolution of hematomas has been performed, using Mössbauer spectrometry and complementary technics (ESR and visible absorption spectrophotometry). The change, in the course of time, of HbO2 in deoxyhemoglobin Hb and other denaturation products (MHb, hemi- and hemochromes,…) are well-recognized on the different spectra. T 1 and T 2 NMR relaxation times are measured in the same time and their shortening is related to the appearance of the paramagnetic denaturation blood compounds.
Culture and biology in the origins of linguistic structure.
Kirby, Simon
2017-02-01
Language is systematically structured at all levels of description, arguably setting it apart from all other instances of communication in nature. In this article, I survey work over the last 20 years that emphasises the contributions of individual learning, cultural transmission, and biological evolution to explaining the structural design features of language. These 3 complex adaptive systems exist in a network of interactions: individual learning biases shape the dynamics of cultural evolution; universal features of linguistic structure arise from this cultural process and form the ultimate linguistic phenotype; the nature of this phenotype affects the fitness landscape for the biological evolution of the language faculty; and in turn this determines individuals' learning bias. Using a combination of computational simulation, laboratory experiments, and comparison with real-world cases of language emergence, I show that linguistic structure emerges as a natural outcome of cultural evolution once certain minimal biological requirements are in place.
Nanocluster irradiation evolution in Fe-9%Cr ODS and ferritic-martensitic alloys
NASA Astrophysics Data System (ADS)
Swenson, M. J.; Wharry, J. P.
2017-12-01
The objective of this study is to evaluate the influence of dose rate and cascade morphology on nanocluster evolution in a model Fe-9%Cr oxide dispersion strengthened steel and the commercial ferritic/martensitic (F/M) alloys HCM12A and HT9. We present a large, systematic data set spanning the three alloys, three irradiating particle types, four orders of magnitude in dose rate, and doses ranging 1-100 displacements per atom over 400-500 °C. Nanoclusters are characterized using atom probe tomography. ODS oxide nanoclusters experience partial dissolution after irradiation due to inverse Ostwald ripening, while F/M nanoclusters undergo Ostwald ripening. Damage cascade morphology is indicative of nanocluster number density evolution. Finally, the effects of dose rate on nanocluster morphology provide evidence for a temperature dilation theory, which purports that a negative temperature shift is necessary for higher dose rate irradiations to emulate nanocluster evolution in lower dose rate irradiations.
Evolution of mare basalts - The complexity of the U-Th-Pb system
NASA Technical Reports Server (NTRS)
Unruh, D. M.; Tatsumoto, M.
1977-01-01
An attempt has been made to gain more insight into mare-basalt evolution by performing a very detailed leaching and mineral-separation U-Th-Pb systematics study on mare basalt 15085. It is found that about 20-50% of the U, Th, and Pb reside on the grain boundaries or in the mesostasis and that the Pb-207/Pb-206 ratios of the grain boundaries and crystal interiors are distinctly different. These distinct trends appear to represent either continuous or episodic postcrystallizational disturbances to the U-Th-Pb system of this rock. Using U and Pb partition coefficients, it is concluded that existing two- and three-stage U-Pb evolution models do not accurately describe mare-basalt genesis. An alternative two-stage + KREEP mixing model is proposed as a simple approximation to U-Pb evolution in lunar rocks. Most Rb-Sr and Sm-Nd data are compatible with this model.
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...
In vitro selection of RNA aptamer specific to Salmonella typhimurium.
Han, Seung Ryul; Lee, Seong-Wook
2013-06-28
Salmonella is a major foodborne pathogen that causes a variety of human diseases. Development of ligands directly and specifically binding to the Salmonella will be crucial for the rapid detection of, and thus for efficient protection from, the virulent bacteria. In this study, we identified a RNA aptamer-based ligand that can specifically recognize Salmonella Typhimurium through SELEX technology. To this end, we isolated and characterized an RNase-resistant RNA aptamer that bound to the OmpC protein of Salmonella Typhimurium with high specificity and affinity (Kd ~ 20 nM). Of note, the selected aptamer was found to specifically bind to Salmonella Typhimurium, but neither to Gram-positive bacteria (Staphylococcus aureus) nor to other Gram-negative bacteria (Escherichia coli O157:H7). This was evinced by aptamer-immobilized ELISA and aptamer-linked precipitation experiments. This Salmonella species-specific aptamer could be useful as a diagnostic ligand against pathogen-caused foodborne sickness.
Development of Single-Stranded DNA Aptamers for Specific Bisphenol A Detection
Jo, Minjoung; Ahn, Ji-Young; Lee, Joohyung; Lee, Seram; Hong, Sun Woo; Yoo, Jae-Wook; Kang, Jeehye; Dua, Pooja
2011-01-01
The development of reagents with high affinity and specificity to small molecules is crucial for the high-throughput detection of chemical compounds, such as toxicants or pollutants. Aptamers are short and single-stranded (ss) oligonucleotides able to recognize target molecules with high affinity. Here, we report the selection of ssDNA aptamers that bind to Bisphenol A (BPA), an environmental hormone. Using SELEX process, we isolated high affinity aptamers to BPA from a 1015 random library of 60 mer ssDNAs. The selected aptamers bound specifically to BPA, but not to structurally similar molecules, such as Bisphenol B with one methyl group difference, or 4,4′-Bisphenol with 2 methyl groups difference. Using these aptamers, we developed an aptamer-based sol–gel biochip and detected BPA dissolved in water. This novel BPA aptamer-based detection can be further applied to the universal and high-specificity detection of small molecules. PMID:21413891
Selection of the simplest RNA that binds isoleucine
LOZUPONE, CATHERINE; CHANGAYIL, SHANKAR; MAJERFELD, IRENE; YARUS, MICHAEL
2003-01-01
We have identified the simplest RNA binding site for isoleucine using selection-amplification (SELEX), by shrinking the size of the randomized region until affinity selection is extinguished. Such a protocol can be useful because selection does not necessarily make the simplest active motif most prominent, as is often assumed. We find an isoleucine binding site that behaves exactly as predicted for the site that requires fewest nucleotides. This UAUU motif (16 highly conserved positions; 27 total), is also the most abundant site in successful selections on short random tracts. The UAUU site, now isolated independently at least 63 times, is a small asymmetric internal loop. Conserved loop sequences include isoleucine codon and anticodon triplets, whose nucleotides are required for amino acid binding. This reproducible association between isoleucine and its coding sequences supports the idea that the genetic code is, at least in part, a stereochemical residue of the most easily isolated RNA–amino acid binding structures. PMID:14561881
Firefly: A HOT camera core for thermal imagers with enhanced functionality
NASA Astrophysics Data System (ADS)
Pillans, Luke; Harmer, Jack; Edwards, Tim
2015-06-01
Raising the operating temperature of mercury cadmium telluride infrared detectors from 80K to above 160K creates new applications for high performance infrared imagers by vastly reducing the size, weight and power consumption of the integrated cryogenic cooler. Realizing the benefits of Higher Operating Temperature (HOT) requires a new kind of infrared camera core with the flexibility to address emerging applications in handheld, weapon mounted and UAV markets. This paper discusses the Firefly core developed to address these needs by Selex ES in Southampton UK. Firefly represents a fundamental redesign of the infrared signal chain reducing power consumption and providing compatibility with low cost, low power Commercial Off-The-Shelf (COTS) computing technology. This paper describes key innovations in this signal chain: a ROIC purpose built to minimize power consumption in the proximity electronics, GPU based image processing of infrared video, and a software customisable infrared core which can communicate wirelessly with other Battlespace systems.
Mechanical Mounting and Adhesive Junction for Large Quartz Optics Operatng at Cryogenic Temperature
NASA Astrophysics Data System (ADS)
Pellizzari, M.; Mosciarello, P.
2012-07-01
Gaia is a global space astrometry mission, with the goal to make the largest, most precise three-dimensional map of our Galaxy. Gaia contains two optical telescopes: in front of their Focal Plane Assembly -FPA- two narrow quartz prisms are mounted for spectrophotometer science: the Blue and Red Photometer Prisms -BPP and RPP-. They are framed in a SiC structure by means of brackets and adhesive junctions between metal parts and quartz optical elements. SELEX GALILEO developed this project as subcontractor of Astrium France. The assembly has to withstand thermoelastic loads due to CTE mismatch at an operative temperature of 120 K. The mechanical mountings design to reduce the stresses due to thermal loads on the adhesive joint is described and the results of the bonding qualification process as well as the flight hardware bonding results are reported.
By-Product Formation in Repetitive PCR Amplification of DNA Libraries during SELEX
Tolle, Fabian; Wilke, Julian; Wengel, Jesper; Mayer, Günter
2014-01-01
The selection of nucleic acid aptamers is an increasingly important approach to generate specific ligands binding to virtually any molecule of choice. However, selection-inherent amplification procedures are prone to artificial by-product formation that prohibits the enrichment of target-recognizing aptamers. Little is known about the formation of such by-products when employing nucleic acid libraries as templates. We report on the formation of two different forms of by-products, named ladder- and non-ladder-type observed during repetitive amplification in the course of in vitro selection experiments. Based on sequence information and the amplification behaviour of defined enriched nucleic acid molecules we suppose a molecular mechanism through which these amplification by-products are built. Better understanding of these mechanisms might help to find solutions minimizing by-product formation and improving the success rate of aptamer selection. PMID:25490402
Quantifying the Number of Independent Organelle DNA Insertions in Genome Evolution and Human Health.
Hazkani-Covo, Einat; Martin, William F
2017-05-01
Fragments of organelle genomes are often found as insertions in nuclear DNA. These fragments of mitochondrial DNA (numts) and plastid DNA (nupts) are ubiquitous components of eukaryotic genomes. They are, however, often edited out during the genome assembly process, leading to systematic underestimation of their frequency. Numts and nupts, once inserted, can become further fragmented through subsequent insertion of mobile elements or other recombinational events that disrupt the continuity of the inserted sequence relative to the genuine organelle DNA copy. Because numts and nupts are typically identified through sequence comparison tools such as BLAST, disruption of insertions into smaller fragments can lead to systematic overestimation of numt and nupt frequencies. Accurate identification of numts and nupts is important, however, both for better understanding of their role during evolution, and for monitoring their increasingly evident role in human disease. Human populations are polymorphic for 141 numt loci, five numts are causal to genetic disease, and cancer genomic studies are revealing an abundance of numts associated with tumor progression. Here, we report investigation of salient parameters involved in obtaining accurate estimates of numt and nupt numbers in genome sequence data. Numts and nupts from 44 sequenced eukaryotic genomes reveal lineage-specific differences in the number, relative age and frequency of insertional events as well as lineage-specific dynamics of their postinsertional fragmentation. Our findings outline the main technical parameters influencing accurate identification and frequency estimation of numts in genomic studies pertinent to both evolution and human health. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
Evolution of Management Thought in the Ancient Times.
ERIC Educational Resources Information Center
Sharma, C. L.
This paper argues that although systematic management thought is a distinctly modern development, the writings of ancient scholars and records of ancient rulers infer that they understood the rudiments of management principles and concepts. To support this thesis, the author reviews the evidence of management practices and concepts in various…
Aquatic invasive species are one of the major ecological threats to the ecological integrity of estuarine and near-coastal waters. However, lack of systematic inventories of nonindigenous species across the North Pacific countries limits our ability to assess how the extent of i...
A sort of revolution: Systematics and physical anthropology in the 20th century.
Cartmill, Matt
2018-04-01
During the first four decades of the 20th century, a system of ideas about the evolution and systematics of humans and other primates coalesced around the work of George Gaylord Simpson and W. E. Le Gros Clark. Buttressed by the "new physical anthropology" of the 1950s, that system provided an authoritative model-a disciplinary matrix or paradigm-for the practice of that aspect of biological anthropology. The Simpson-Le Gros Clark synthesis began to unravel in the 1960s and collapsed in the 1970s under the onslaught of cladistic systematics. The cladistic "revolution" resembles a paradigm shift of the sort proposed by Thomas Kuhn because it was driven, not by new biological discoveries or theories, but by a change in aesthetics. © 2017 Wiley Periodicals, Inc.
Indications of a spatial variation of the fine structure constant.
Webb, J K; King, J A; Murphy, M T; Flambaum, V V; Carswell, R F; Bainbridge, M B
2011-11-04
We previously reported Keck telescope observations suggesting a smaller value of the fine structure constant α at high redshift. New Very Large Telescope (VLT) data, probing a different direction in the Universe, shows an inverse evolution; α increases at high redshift. Although the pattern could be due to as yet undetected systematic effects, with the systematics as presently understood the combined data set fits a spatial dipole, significant at the 4.2 σ level, in the direction right ascension 17.5 ± 0.9 h, declination -58 ± 9 deg. The independent VLT and Keck samples give consistent dipole directions and amplitudes, as do high and low redshift samples. A search for systematics, using observations duplicated at both telescopes, reveals none so far which emulate this result.
Evolution of Inclusions During 1473 K Heating Process in EH36 Shipbuilding Steel with Mg Addition
NASA Astrophysics Data System (ADS)
Wang, Qiyu; Zou, Xiaodong; Matsuura, Hiroyuki; Wang, Cong
2018-04-01
Inclusion evolution behaviors of EH36 shipbuilding steel with Mg addition were systematically investigated during a 1473 K heating process by means of ex situ SEM examination and in situ CSLM observations. It has been shown that individual MnS inclusions are the dominating phase in the cast billet. However, their number density decreases substantially after heating, while the density of MnS and oxides combined type inclusions is on the rise. In addition, coarsening, split and movement behaviors of MnS inclusions at high temperature are demonstrated here.
Evolution of Inclusions During 1473 K Heating Process in EH36 Shipbuilding Steel with Mg Addition
NASA Astrophysics Data System (ADS)
Wang, Qiyu; Zou, Xiaodong; Matsuura, Hiroyuki; Wang, Cong
2017-12-01
Inclusion evolution behaviors of EH36 shipbuilding steel with Mg addition were systematically investigated during a 1473 K heating process by means of ex situ SEM examination and in situ CSLM observations. It has been shown that individual MnS inclusions are the dominating phase in the cast billet. However, their number density decreases substantially after heating, while the density of MnS and oxides combined type inclusions is on the rise. In addition, coarsening, split and movement behaviors of MnS inclusions at high temperature are demonstrated here.
Fast sub-electron detectors review for interferometry
NASA Astrophysics Data System (ADS)
Feautrier, Philippe; Gach, Jean-Luc; Bério, Philippe
2016-08-01
New disruptive technologies are now emerging for detectors dedicated to interferometry. The detectors needed for this kind of applications need antonymic characteristics: the detector noise must be very low, especially when the signal is dispersed but at the same time must also sample the fast temporal characteristics of the signal. This paper describes the new fast low noise technologies that have been recently developed for interferometry and adaptive optics. The first technology is the Avalanche PhotoDiode (APD) infrared arrays made of HgCdTe. In this paper are presented the two programs that have been developed in that field: the Selex Saphira 320x256 [1] and the 320x255 RAPID detectors developed by Sofradir/CEA LETI in France [2], [3], [4]. Status of these two programs and future developments are presented. Sub-electron noise can now be achieved in the infrared using this technology. The exceptional characteristics of HgCdTe APDs are due to a nearly exclusive impaction ionization of the electrons, and this is why these devices have been called "electrons avalanche photodiodes" or e-APDs. These characteristics have inspired a large effort in developing focal plan arrays using HgCdTe APDs for low photon number applications such as active imaging in gated mode (2D) and/or with direct time of flight detection (3D imaging) and, more recently, passive imaging for infrared wave front correction and fringe tracking in astronomical observations. In addition, a commercial camera solution called C-RED, based on Selex Saphira and commercialized by First Light Imaging [5], is presented here. Some groups are also working with instruments in the visible. In that case, another disruptive technology is showing outstanding performances: the Electron Multiplying CCDs (EMCCD) developed mainly by e2v technologies in UK. The OCAM2 camera, commercialized by First Light Imaging [5], uses the 240x240 EMMCD from e2v and is successfully implemented on the VEGA instrument on the CHARA interferometer (US) by the Lagrange laboratory from Observatoire de la Cote d'Azur. By operating the detector at gain 1000, the readout noise is as low as 0.1 e and data can be analyzed with a better contrast in photon counting mode.
GIADA On-Board Rosetta: Early Dust Grain Detections and Dust Coma Characterization of Comet 67P/C-G
NASA Astrophysics Data System (ADS)
Rotundi, A.; Della Corte, V.; Accolla, M.; Ferrari, M.; Ivanovski, S.; Lucarelli, F.; Mazzotta Epifani, E.; Sordini, R.; Palumbo, P.; Colangeli, L.; Lopez-Moreno, J. J.; Rodriguez, J.; Fulle, M.; Bussoletti, E.; Crifo, J. F.; Esposito, F.; Green, S.; Grün, E.; Lamy, P. L.; McDonnell, T.; Mennella, V.; Molina, A.; Moreno, F.; Ortiz, J. L.; Palomba, E.; Perrin, J. M.; Rodrigo, R.; Weissman, P. R.; Zakharov, V.; Zarnecki, J.
2014-12-01
GIADA (Grain Impact Analyzer and Dust Accumulator) flying on-board Rosetta is devoted to study the cometary dust environment of 67P/Churiumov-Gerasimenko. GIADA is composed of 3 sub-systems: the GDS (Grain Detection System), based on grain detection through light scattering; an IS (Impact Sensor), giving momentum measurement detecting the impact on a sensed plate connected with 5 piezoelectric sensors; the MBS (MicroBalances System), constituted of 5 Quartz Crystal Microbalances (QCMs), giving cumulative deposited dust mass by measuring the variations of the sensors' frequency. The combination of the measurements performed by these 3 subsystems provides: the number, the mass, the momentum and the velocity distribution of dust grains emitted from the cometary nucleus.No prior in situ dust dynamical measurements at these close distances from the nucleus and starting from such large heliocentric distances are available up to date. We present here the first results obtained from the beginning of the Rosetta scientific phase. We will report dust grains early detection at about 800 km from the nucleus in August 2014 and the following measurements that allowed us characterizing the 67P/C-G dust environment at distances less than 100 km from the nucleus and single grains dynamical properties. Acknowledgements. GIADA was built by a consortium led by the Univ. Napoli "Parthenope" & INAF-Oss. Astr. Capodimonte, IT, in collaboration with the Inst. de Astrofisica de Andalucia, ES, Selex-ES s.p.a. and SENER. GIADA is presently managed & operated by Ist. di Astrofisica e Planetologia Spaziali-INAF, IT. GIADA was funded and managed by the Agenzia Spaziale Italiana, IT, with a support of the Spanish Ministry of Education and Science MEC, ES. GIADA was developped from a PI proposal supported by the University of Kent; sci. & tech. contribution given by CISAS, IT, Lab. d'Astr. Spat., FR, and Institutions from UK, IT, FR, DE and USA. We thank the RSGS/ESAC, RMOC/ESOC & Rosetta Project/ESTEC for their outstanding work. Science support provided by NASA through the US Rosetta Project managed by JPL/California Institute of Technology. GIADA calibrated data will be available through the ESA's PSA web site (www.rssd.esa.int/index.php?project=PSA&page=index). Thanks Angioletta.
Biophysics and bioinformatics of transcription regulation in bacteria and bacteriophages
NASA Astrophysics Data System (ADS)
Djordjevic, Marko
2005-11-01
Due to rapid accumulation of biological data, bioinformatics has become a very important branch of biological research. In this thesis, we develop novel bioinformatic approaches and aid design of biological experiments by using ideas and methods from statistical physics. Identification of transcription factor binding sites within the regulatory segments of genomic DNA is an important step towards understanding of the regulatory circuits that control expression of genes. We propose a novel, biophysics based algorithm, for the supervised detection of transcription factor (TF) binding sites. The method classifies potential binding sites by explicitly estimating the sequence-specific binding energy and the chemical potential of a given TF. In contrast with the widely used information theory based weight matrix method, our approach correctly incorporates saturation in the transcription factor/DNA binding probability. This results in a significant reduction in the number of expected false positives, and in the explicit appearance---and determination---of a binding threshold. The new method was used to identify likely genomic binding sites for the Escherichia coli TFs, and to examine the relationship between TF binding specificity and degree of pleiotropy (number of regulatory targets). We next address how parameters of protein-DNA interactions can be obtained from data on protein binding to random oligos under controlled conditions (SELEX experiment data). We show that 'robust' generation of an appropriate data set is achieved by a suitable modification of the standard SELEX procedure, and propose a novel bioinformatic algorithm for analysis of such data. Finally, we use quantitative data analysis, bioinformatic methods and kinetic modeling to analyze gene expression strategies of bacterial viruses. We study bacteriophage Xp10 that infects rice pathogen Xanthomonas oryzae. Xp10 is an unusual bacteriophage, which has morphology and genome organization that most closely resembles temperate phages, such as lambda. It, however, encodes its own T7-like RNA polymerase (characteristic of virulent phages), whose role in gene expression was unclear. Our analysis resulted in quantitative understanding of the role of both host and phage RNA polymerase, and in the identification of the previously unknown promoter sequence for Xp10 RNA polymerase. More generally, an increasing number of phage genomes are being sequenced every year, and we expect that methods of quantitative data analysis that we introduced will provide an efficient way to study gene expression strategies of novel bacterial viruses.
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
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.
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.
Speltini, Andrea; Sturini, Michela; Dondi, Daniele; Annovazzi, Enrico; Maraschi, Federica; Caratto, Valentina; Profumo, Antonella; Buttafava, Armando
2014-10-01
This work presents a systematic study of cellulose (CLS) as a sacrificial biomass for photocatalytic H2 evolution from water. The idea is indeed to couple a largely available and not expensive biomass, and water, with a renewable energy like solar radiation. An aqueous CLS suspension irradiated either at 366 nm (UV-A) or under sunlight in the presence of Pt/TiO2 behaves as a H2 evolving system. The effects of irradiation time, catalyst and CLS concentrations, pH and water salinity are studied. Addition of CLS to the sample significantly improved H2 evolution from water splitting, with yields up to ten fold higher than those observed in neat water. The mechanism of the photocatalytic process relies on the TiO2-mediated CLS hydrolysis, under irradiation. The polysaccharide depolymerisation generates water-soluble species and intermediates, among them 5-hydroxymethylfurfural (HMF) was identified. These intermediates are readily oxidized following the glucose photoreforming, thus enhancing water hydrogen ion reduction to give gas-phase H2. The formation of "colored" by-products from HMF self-polymerization involves a sort of "in situ dye sensitization" that allows an effective photoreaction even under solar light. The procedure is evaluated and successfully extended on cellulosic biomasses, i.e. rice husk and alfalfa (Medicago sativa) stems, not previously investigated for this application.
Galaxies at redshifts 5 to 6 with systematically low dust content and high [C II] emission
NASA Astrophysics Data System (ADS)
Capak, P. L.; Carilli, C.; Jones, G.; Casey, C. M.; Riechers, D.; Sheth, K.; Carollo, C. M.; Ilbert, O.; Karim, A.; Lefevre, O.; Lilly, S.; Scoville, N.; Smolcic, V.; Yan, L.
2015-06-01
The rest-frame ultraviolet properties of galaxies during the first three billion years of cosmic time (redshift z > 4) indicate a rapid evolution in the dust obscuration of such galaxies. This evolution implies a change in the average properties of the interstellar medium, but the measurements are systematically uncertain owing to untested assumptions and the inability to detect heavily obscured regions of the galaxies. Previous attempts to measure the interstellar medium directly in normal galaxies at these redshifts have failed for a number of reasons, with two notable exceptions. Here we report measurements of the forbidden C II emission (that is, [C II]) from gas, and the far-infrared emission from dust, in nine typical star-forming galaxies about one billion years after the Big Bang (z ~ 5-6). We find that these galaxies have thermal emission that is less than 1/12 that of similar systems about two billion years later, and enhanced [C II] emission relative to the far-infrared continuum, confirming a strong evolution in the properties of the interstellar medium in the early Universe. The gas is distributed over scales of one to eight kiloparsecs, and shows diverse dynamics within the sample. These results are consistent with early galaxies having significantly less dust than typical galaxies seen at z < 3 and being comparable in dust content to local low-metallicity systems.
Galaxies at redshifts 5 to 6 with systematically low dust content and high [C II] emission.
Capak, P L; Carilli, C; Jones, G; Casey, C M; Riechers, D; Sheth, K; Carollo, C M; Ilbert, O; Karim, A; LeFevre, O; Lilly, S; Scoville, N; Smolcic, V; Yan, L
2015-06-25
The rest-frame ultraviolet properties of galaxies during the first three billion years of cosmic time (redshift z > 4) indicate a rapid evolution in the dust obscuration of such galaxies. This evolution implies a change in the average properties of the interstellar medium, but the measurements are systematically uncertain owing to untested assumptions and the inability to detect heavily obscured regions of the galaxies. Previous attempts to measure the interstellar medium directly in normal galaxies at these redshifts have failed for a number of reasons, with two notable exceptions. Here we report measurements of the forbidden C ii emission (that is, [C II]) from gas, and the far-infrared emission from dust, in nine typical star-forming galaxies about one billion years after the Big Bang (z ≈ 5-6). We find that these galaxies have thermal emission that is less than 1/12 that of similar systems about two billion years later, and enhanced [C II] emission relative to the far-infrared continuum, confirming a strong evolution in the properties of the interstellar medium in the early Universe. The gas is distributed over scales of one to eight kiloparsecs, and shows diverse dynamics within the sample. These results are consistent with early galaxies having significantly less dust than typical galaxies seen at z < 3 and being comparable in dust content to local low-metallicity systems.
NASA Astrophysics Data System (ADS)
Collins, John; Rogers, Ted
2015-04-01
There is considerable controversy about the size and importance of nonperturbative contributions to the evolution of transverse-momentum-dependent (TMD) parton distribution functions. Standard fits to relatively high-energy Drell-Yan data give evolution that when taken to lower Q is too rapid to be consistent with recent data in semi-inclusive deeply inelastic scattering. Some authors provide very different forms for TMD evolution, even arguing that nonperturbative contributions at large transverse distance bT are not needed or are irrelevant. Here, we systematically analyze the issues, both perturbative and nonperturbative. We make a motivated proposal for the parametrization of the nonperturbative part of the TMD evolution kernel that could give consistency: with the variety of apparently conflicting data, with theoretical perturbative calculations where they are applicable, and with general theoretical nonperturbative constraints on correlation functions at large distances. We propose and use a scheme- and scale-independent function A (bT) that gives a tool to compare and diagnose different proposals for TMD evolution. We also advocate for phenomenological studies of A (bT) as a probe of TMD evolution. The results are important generally for applications of TMD factorization. In particular, they are important to making predictions for proposed polarized Drell-Yan experiments to measure the Sivers function.
Zhou, Xiaorun; Lu, Taiping; Zhu, Yadan; Zhao, Guangzhou; Dong, Hailiang; Jia, Zhigang; Yang, Yongzhen; Chen, Yongkang; Xu, Bingshe
2017-12-01
Surface morphology evolution mechanisms of InGaN/GaN multiple quantum wells (MQWs) during GaN barrier growth with different hydrogen (H 2 ) percentages have been systematically studied. Ga surface-diffusion rate, stress relaxation, and H 2 etching effect are found to be the main affecting factors of the surface evolution. As the percentage of H 2 increases from 0 to 6.25%, Ga surface-diffusion rate and the etch effect are gradually enhanced, which is beneficial to obtaining a smooth surface with low pits density. As the H 2 proportion further increases, stress relaxation and H 2 over- etching effect begin to be the dominant factors, which degrade surface quality. Furthermore, the effects of surface evolution on the interface and optical properties of InGaN/GaN MQWs are also profoundly discussed. The comprehensive study on the surface evolution mechanisms herein provides both technical and theoretical support for the fabrication of high-quality InGaN/GaN heterostructures.
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.
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.
Liberati, Alessandro; Altman, Douglas G; Tetzlaff, Jennifer; Mulrow, Cynthia; Gøtzsche, Peter C; Ioannidis, John P A; Clarke, Mike; Devereaux, P J; Kleijnen, Jos; Moher, David
2009-01-01
Systematic reviews and meta-analyses are essential to summarise evidence relating to efficacy and safety of healthcare interventions accurately and reliably. The clarity and transparency of these reports, however, are not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (quality of reporting of meta-analysis) statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realising these issues, an international group that included experienced authors and methodologists developed PRISMA (preferred reporting items for systematic reviews and meta-analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this explanation and elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA statement, this document, and the associated website (www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses. PMID:19622552
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.
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.
A Model of the Temporal Dynamics of Knowledge Brokerage in Sustainable Development
ERIC Educational Resources Information Center
Hukkinen, Janne I.
2016-01-01
I develop a conceptual model of the temporal dynamics of knowledge brokerage for sustainable development. Brokerage refers to efforts to make research and policymaking more accessible to each other. The model enables unbiased and systematic consideration of knowledge brokerage as part of policy evolution. The model is theoretically grounded in…
Towards a Caring Community: Modeling, Dialogue, Practice, and Confirmation.
ERIC Educational Resources Information Center
Harris, Charlotte Matthews
A teacher educator, engaged in ongoing practitioner inquiry to explore self as well as program, examines her evolution as a teacher of teachers through reflection, systematic inquiry, and collaboration. Relating autobiographically, she conjures up her professional stories and listens to her voice in an effort to define and refine her role, reflect…
ERIC Educational Resources Information Center
Shogren, Karrie A.
2013-01-01
In light of the rapid evolution of research, policy, and practice in the intellectual disability (ID) field resulting from shifts in our conceptualization of disability and in frameworks for the diagnosis and classification of ID, systematic consideration of the multiple, interrelated contextual factors that impact research, policy, and practice…
ERIC Educational Resources Information Center
deLisle, Lee
2009-01-01
"Creating Special Events" is organized as a systematic approach to festivals and events for students who seek a career in event management. This book looks at the evolution and history of festivals and events and proceeds to the nuts and bolts of event management. The book presents event management as the means of planning, organizing, directing,…
Creativity, Magic and Morality: The Dilemma of the Young Gifted Child.
ERIC Educational Resources Information Center
Buescher, Thomas M.
1979-01-01
The article explores the dilemma of young gifted children (ages 4-8 years) in the evolution and resolution of their own system of morality. The author explains that research and observation has revealed a systematic appearance and disappearance of magical thinking (the hallmark of the onset of reasoning) in four stages. (PHR)
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…
NASA Astrophysics Data System (ADS)
Pazó, Diego; Rodríguez, Miguel A.; López, Juan M.
2010-05-01
We study the evolution of finite perturbations in the Lorenz ‘96 model, a meteorological toy model of the atmosphere. The initial perturbations are chosen to be aligned along different dynamic vectors: bred, Lyapunov, and singular vectors. Using a particular vector determines not only the amplification rate of the perturbation but also the spatial structure of the perturbation and its stability under the evolution of the flow. The evolution of perturbations is systematically studied by means of the so-called mean-variance of logarithms diagram that provides in a very compact way the basic information to analyse the spatial structure. We discuss the corresponding advantages of using those different vectors for preparing initial perturbations to be used in ensemble prediction systems, focusing on key properties: dynamic adaptation to the flow, robustness, equivalence between members of the ensemble, etc. Among all the vectors considered here, the so-called characteristic Lyapunov vectors are possibly optimal, in the sense that they are both perfectly adapted to the flow and extremely robust.
NASA Astrophysics Data System (ADS)
Pazó, Diego; Rodríguez, Miguel A.; López, Juan M.
2010-01-01
We study the evolution of finite perturbations in the Lorenz `96 model, a meteorological toy model of the atmosphere. The initial perturbations are chosen to be aligned along different dynamic vectors: bred, Lyapunov, and singular vectors. Using a particular vector determines not only the amplification rate of the perturbation but also the spatial structure of the perturbation and its stability under the evolution of the flow. The evolution of perturbations is systematically studied by means of the so-called mean-variance of logarithms diagram that provides in a very compact way the basic information to analyse the spatial structure. We discuss the corresponding advantages of using those different vectors for preparing initial perturbations to be used in ensemble prediction systems, focusing on key properties: dynamic adaptation to the flow, robustness, equivalence between members of the ensemble, etc. Among all the vectors considered here, the so-called characteristic Lyapunov vectors are possibly optimal, in the sense that they are both perfectly adapted to the flow and extremely robust.
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.
2013-01-01
Cochrane systematic reviews have proven to be beneficial for decision making processes, both on a practitioner and a policy level, and there are current initiatives to extend the types of evidence used by them, including qualitative research. In this article we outline the major achievements of the Cochrane Qualitative and Implementation Methods Group. Although the Group has encountered numerous challenges in dealing with the evolution of qualitative evidence synthesis, both outside and within the Cochrane Collaboration, it has successfully responded to the challenges posed in terms of incorporating qualitative evidence in systematic reviews. The Methods Group will continue to advocate for more flexible and inclusive approaches to evidence synthesis in order to meet the exciting challenges and opportunities presented by mixed methods systematic reviews and reviews of complex interventions. PMID:24135194
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hosokawa, Takashi; Offner, Stella S. R.; Krumholz, Mark R., E-mail: Takashi.Hosokawa@jpl.nasa.gov, E-mail: hosokwtk@gmail.com
2011-09-10
We revisit the problem of low-mass pre-main-sequence stellar evolution and its observational consequences for where stars fall on the Hertzsprung-Russell diagram (HRD). In contrast to most previous work, our models follow stars as they grow from small masses via accretion, and we perform a systematic study of how the stars' HRD evolution is influenced by their initial radius, by the radiative properties of the accretion flow, and by the accretion history, using both simple idealized accretion histories and histories taken from numerical simulations of star cluster formation. We compare our numerical results to both non-accreting isochrones and to the positionsmore » of observed stars in the HRD, with a goal of determining whether both the absolute ages and the age dispersions inferred from non-accreting isochrones are reliable. We show that non-accreting isochrones can sometimes overestimate stellar ages for more massive stars (those with effective temperatures above {approx}3500 K), thereby explaining why non-accreting isochrones often suggest a systematic age difference between more and less massive stars in the same cluster. However, we also find the only way to produce a similar overestimate for the ages of cooler stars is if these stars grow from {approx}0.01 M{sub sun} seed protostars that are an order of magnitude smaller than predicted by current theoretical models, and if the size of the seed protostar correlates systematically with the final stellar mass at the end of accretion. We therefore conclude that, unless both of these conditions are met, inferred ages and age spreads for cool stars are reliable, at least to the extent that the observed bolometric luminosities and temperatures are accurate. Finally, we note that the time dependence of the mass accretion rate has remarkably little effect on low-mass stars' evolution on the HRD, and that such time dependence may be neglected for all stars except those with effective temperatures above {approx}4000 K.« less
Updates in the IR responsivity of VIR, the spectrometer of the Dawn mission.
NASA Astrophysics Data System (ADS)
Ammannito, Eleonora; Mc Cord, Thomas B.; De Sanctis, Maria Cristina.; Combe, Jean-Philippe
VIR-MS (Visual and Infrared Mapping Spectrometer) is the imaging spectrometer of the Dawn mission (1,2). Here, first we describe the computation of a new instrument responsivity based on the internal calibration data acquired during the operations at Vesta, and then we describe its effect on the dataset and on the results published so far. VIR-MS was built in Italy by a scientific-industrial (IAPS/INAF in Rome (Italy) and Selex ES in Campi Bisenzio (Fi, Italy)) consortium financially supported by the Italian Space Agency. VIR-MS is an high spatial resolution spectrometer (FOV of 64mrad, IFOV of 250 µrad) in the 0.25-5 µm range with an IFOV of 250 µrad and a spectral sampling of about 2 nm in the visible range and 10 nm in the IR range. The results of the on-ground calibration held in the Selex calibration facility in September 2005 were already presented and discussed in a paper (2). This version has been used to calibrate the data available on the Planetary Data System (PDS) Small Bodies Node, dataset used in all the papers published so far. However, after the operations at the asteroid Vesta, we have identified some artifacts in the instrument responsivity in the 2.5-3.5 µm region, which is where several absorption bands of OH and H2O occur. Those artifacts were systematic, and therefore they did not prevent the detection of relative spectral variations associated to OH and H2O. Actually, the only paper published in which are discussed spectra in this range (3) used a different calibration method described in the paper itself. This method used a simple correction of the response function based on an empirical calibration correction that is appropriate to recover the signal in that specific range. However, the absolute absorption band depth of OH and H2O could not be calculated. To compute a new instrument responsivity we used the internal lamp of the spectrometer. This lamp, made of a tungsten filament, is characterized by a blackbody-like emission at about 2400K (4). Since the spectrum of the infrared radiation emitted by the tungsten filaments is featureless, a polystyrene filter was inserted for a wavelength calibration of the IR channel. The idea was to use the black body radiation of this lamp to retrieve a relative Instrument Responsivity in the 2.5-3.5 µm region. First we calibrated the signal from internal calibration lamp with the on-ground responsivity, and then we retrieved the equivalent temperature of the radiation fitting a Planck curve. The next step was to compute the Planck function at the equivalent temperature. The new Instrument Responsivity is the result of the ratio between the raw signal of the lamp and the Planck function. This ratio must be multiplied by a factor to take into account the integration time used to acquire the signal, the transmittance of the polystyrene filter, and the viewing geometry. The new instrument responsivity function minimizes most calibration residuals that was showing as artifact peaks between 2.5 and 2.9 µm in the previous calibration. It now allows the use of VIR spectra to identify absorption bands of OH and H2O, without requiring additional empirical corrections. As calibration is always an on-going process, we are looking forward to enable the interpretation of absolute absorption band depths, which is a required step for the calculation of surface material abundances. References: (1) C.T. Russell & C.A. Raymond, Space Sci. Rev., 163, 3 2011 (2) M.C. De Sanctis, A. Coradini, E. Ammannito, E., et al. Space Sci. Rev.,163, 329, 2011 (3) M.C. DeSanctis, J-Ph. Combe et al APJL 758:L36, 2013 (4)R. Melchiorri, G. Piccioni, A. Mazzoni, Rev. Sci. Instrum. 74(8), 3796-3801 2003
[Systematization of primary headache: current and future prospects].
Odinak, M M; Iskra, D A
2014-02-01
The article is devoted to the current state of the problem of systematization of primary headaches and main clinical forms. The conceptual evolution of ideas about the classification of certain options of cephalgia and identified major trends for its improvement is given. Verification of types and subtypes of individual cephalgia can present a significant challenge even for experienced neurologists, neurosurgeons, and internists. In this regard in most European countries and the US. have set up specialized centers for the treatment of headaches. Concluded that in the short term in the national health care system, including. Including the Armed Forces, it is advisable to create such centers.
Defect evolution and impurity migration in Na-implanted ZnO
NASA Astrophysics Data System (ADS)
Neuvonen, Pekka T.; Vines, Lasse; Venkatachalapathy, Vishnukanthan; Zubiaga, Asier; Tuomisto, Filip; Hallén, Anders; Svensson, Bengt G.; Kuznetsov, Andrej Yu.
2011-11-01
Secondary ion mass spectrometry (SIMS) and positron annihilation spectroscopy (PAS) have been applied to study impurity migration and open volume defect evolution in Na+ implanted hydrothermally grown ZnO samples. In contrast to most other elements, the presence of Na tends to decrease the concentration of open volume defects upon annealing and for temperatures above 600∘C, Na exhibits trap-limited diffusion correlating with the concentration of Li. A dominating trap for the migrating Na atoms is most likely Li residing on Zn site, but a systematic analysis of the data suggests that zinc vacancies also play an important role in the trapping process.
Collins, John; Rogers, Ted
2015-04-01
There is considerable controversy about the size and importance of non-perturbative contributions to the evolution of transverse momentum dependent (TMD) parton distribution functions. Standard fits to relatively high-energy Drell-Yan data give evolution that when taken to lower Q is too rapid to be consistent with recent data in semi-inclusive deeply inelastic scattering. Some authors provide very different forms for TMD evolution, even arguing that non-perturbative contributions at large transverse distance bT are not needed or are irrelevant. Here, we systematically analyze the issues, both perturbative and non-perturbative. We make a motivated proposal for the parameterization of the non-perturbative part ofmore » the TMD evolution kernel that could give consistency: with the variety of apparently conflicting data, with theoretical perturbative calculations where they are applicable, and with general theoretical non-perturbative constraints on correlation functions at large distances. We propose and use a scheme- and scale-independent function A(bT) that gives a tool to compare and diagnose different proposals for TMD evolution. We also advocate for phenomenological studies of A(bT) as a probe of TMD evolution. The results are important generally for applications of TMD factorization. In particular, they are important to making predictions for proposed polarized Drell- Yan experiments to measure the Sivers function.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Collins, John; Rogers, Ted
There is considerable controversy about the size and importance of non-perturbative contributions to the evolution of transverse momentum dependent (TMD) parton distribution functions. Standard fits to relatively high-energy Drell-Yan data give evolution that when taken to lower Q is too rapid to be consistent with recent data in semi-inclusive deeply inelastic scattering. Some authors provide very different forms for TMD evolution, even arguing that non-perturbative contributions at large transverse distance bT are not needed or are irrelevant. Here, we systematically analyze the issues, both perturbative and non-perturbative. We make a motivated proposal for the parameterization of the non-perturbative part ofmore » the TMD evolution kernel that could give consistency: with the variety of apparently conflicting data, with theoretical perturbative calculations where they are applicable, and with general theoretical non-perturbative constraints on correlation functions at large distances. We propose and use a scheme- and scale-independent function A(bT) that gives a tool to compare and diagnose different proposals for TMD evolution. We also advocate for phenomenological studies of A(bT) as a probe of TMD evolution. The results are important generally for applications of TMD factorization. In particular, they are important to making predictions for proposed polarized Drell- Yan experiments to measure the Sivers function.« less
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.
Liberati, Alessandro; Altman, Douglas G.; Tetzlaff, Jennifer; Mulrow, Cynthia; Gøtzsche, Peter C.; Ioannidis, John P. A.; Clarke, Mike; Devereaux, P. J.; Kleijnen, Jos; Moher, David
2009-01-01
Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (QUality Of Reporting Of Meta-analysis) Statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this Explanation and Elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA Statement, this document, and the associated Web site (http://www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses. PMID:19621070
Birds Do It, Bees Do It: Evolution and the Comparative Psychology of Mate Choice
ERIC Educational Resources Information Center
Boothroyd, Lynda G.; McLaughlin, Edward
2011-01-01
The primary theoretical framework for the study of human physical attraction is currently Darwinian sexual selection. Not only has this perspective enabled the discovery of what appear to be strong universals in human mate choice but it has also facilitated our understanding of systematic variation in preferences both between and within…
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…
Establishing Systematic Modular Courses for Key Teaching Competencies of Teachers in Hsinchu City
ERIC Educational Resources Information Center
Cheng, Yuan-Chuan; Chen, Yin-Che; Chiang, Woei-Min; Yang, Chuan-Lien
2015-01-01
The evolution of the Internet, trends in mobile device usage, and changes in the perceptions of city leaders and residents have gradually transformed cities into smart cities. Through a literature review, survey analysis, and focus group interview, this study explored the educational vision and consensus in developing Smart Hsinchu, and analyzed…
ERIC Educational Resources Information Center
Doronila, Maria Luisa C.
In the Philippines, introduction of a formal education system, new written language, and the knowledge encoded in it have been part of a colonization process and not the result of direct evolution from informal education. The discontinuities between formal and informal education--abstraction, systematization, and specialization--are greater and…
Quantifying the Number of Independent Organelle DNA Insertions in Genome Evolution and Human Health
Martin, William F.
2017-01-01
Fragments of organelle genomes are often found as insertions in nuclear DNA. These fragments of mitochondrial DNA (numts) and plastid DNA (nupts) are ubiquitous components of eukaryotic genomes. They are, however, often edited out during the genome assembly process, leading to systematic underestimation of their frequency. Numts and nupts, once inserted, can become further fragmented through subsequent insertion of mobile elements or other recombinational events that disrupt the continuity of the inserted sequence relative to the genuine organelle DNA copy. Because numts and nupts are typically identified through sequence comparison tools such as BLAST, disruption of insertions into smaller fragments can lead to systematic overestimation of numt and nupt frequencies. Accurate identification of numts and nupts is important, however, both for better understanding of their role during evolution, and for monitoring their increasingly evident role in human disease. Human populations are polymorphic for 141 numt loci, five numts are causal to genetic disease, and cancer genomic studies are revealing an abundance of numts associated with tumor progression. Here, we report investigation of salient parameters involved in obtaining accurate estimates of numt and nupt numbers in genome sequence data. Numts and nupts from 44 sequenced eukaryotic genomes reveal lineage-specific differences in the number, relative age and frequency of insertional events as well as lineage-specific dynamics of their postinsertional fragmentation. Our findings outline the main technical parameters influencing accurate identification and frequency estimation of numts in genomic studies pertinent to both evolution and human health. PMID:28444372
The meanings of recovery from addiction: evolution and promises.
El-Guebaly, Nady
2012-03-01
To review the evolution of the paradigm of recovery in addiction and its implications. A systematic literature review was conducted using the MEDLINE and PsychInfo databases over the past 10 years and key references from the retrieved literature. The historical evolution of the concept of recovery has been shaped by several driving forces, including consumer experience, the need to better define our treatment outcome and parallel elaboration of the concepts of health, quality of life, and chronic disorders. Similarities and differences with the concept of "recovery" in mental health and other biomedical fields are identified.The empirical basis is growing in support of various proposed attributions and features of recovery along with the temporal benchmarks involved. The various forms of recovery, such as "natural," "transformational," or "medication-assisted," describe a choice of pathways to a common goal.The management implications are far-reaching and call for system shifts from acute stabilization to sustained recovery, including the growth of alternative institutions, and roles complementary to mutual help. Tools for the sustenance of recovery, including educational kits, recovery workbooks, and e-recovery initiatives, are developing. Although first-person accounts of recovery abound, a more systematic empirical investigation of the concept has just begun, including demographic and cultural differences. Management implications are derived from the experience with other "mainstream" chronic disorders with treatment providing stabilization and initiation of recovery and a range of long-term resources becoming available to sustain it.
NASA Astrophysics Data System (ADS)
Nakamura, Ko; Takiwaki, Tomoya; Kuroda, Takami; Kotake, Kei
2015-12-01
We present an overview of two-dimensional (2D) core-collapse supernova simulations employing a neutrino transport scheme by the isotropic diffusion source approximation. We study 101 solar-metallicity, 247 ultra metal-poor, and 30 zero-metal progenitors covering zero-age main sequence mass from 10.8 M⊙ to 75.0 M⊙. Using the 378 progenitors in total, we systematically investigate how the differences in the structures of these multiple progenitors impact the hydrodynamics evolution. By following a long-term evolution over 1.0 s after bounce, most of the computed models exhibit neutrino-driven revival of the stalled bounce shock at ˜200-800 ms postbounce, leading to the possibility of explosion. Pushing the boundaries of expectations in previous one-dimensional studies, our results confirm that the compactness parameter ξ that characterizes the structure of the progenitors is also a key in 2D to diagnosing the properties of neutrino-driven explosions. Models with high ξ undergo high ram pressure from the accreting matter onto the stalled shock, which affects the subsequent evolution of the shock expansion and the mass of the protoneutron star under the influence of neutrino-driven convection and the standing accretion-shock instability. We show that the accretion luminosity becomes higher for models with high ξ, which makes the growth rate of the diagnostic explosion energy higher and the synthesized nickel mass bigger. We find that these explosion characteristics tend to show a monotonic increase as a function of the compactness parameter ξ.
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
Systematics of strength function sum rules
DOE Office of Scientific and Technical Information (OSTI.GOV)
Johnson, Calvin W.
2015-08-28
Sum rules provide useful insights into transition strength functions and are often expressed as expectation values of an operator. In this letter I demonstrate that non-energy-weighted transition sum rules have strong secular dependences on the energy of the initial state. Such non-trivial systematics have consequences: the simplification suggested by the generalized Brink–Axel hypothesis, for example, does not hold for most cases, though it weakly holds in at least some cases for electric dipole transitions. Furthermore, I show the systematics can be understood through spectral distribution theory, calculated via traces of operators and of products of operators. Seen through this lens,more » violation of the generalized Brink–Axel hypothesis is unsurprising: one expectssum rules to evolve with excitation energy. Moreover, to lowest order the slope of the secular evolution can be traced to a component of the Hamiltonian being positive (repulsive) or negative (attractive).« 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.
Kassam, Daud; Seki, Shingo; Horic, Michio; Yamaoka, Kosaku
2006-08-01
The apparent inter-lake morphological similarity among East African Great Lakes' cichlid species/genera has left evolutionary biologists asking whether such similarity is due to sharing of common ancestor or mere convergent evolution. In order to answer such question, we first used Geometric Morphometrics, GM, to quantify morphological similarity and then subsequently used Amplified Fragment Length Polymorphism, AFLP, to determine if similar morphologies imply shared ancestry or convergent evolution. GM revealed that not all presumed morphological similar pairs were indeed similar, and the dendrogram generated from AFLP data indicated distinct clusters corresponding to each lake and not inter-lake morphological similar pairs. Such results imply that the morphological similarity is due to convergent evolution and not shared ancestry. The congruency of GM and AFLP generated dendrograms imply that GM is capable of picking up phylogenetic signal, and thus GM can be potential tool in phylogenetic systematics.
[Evolution of genomic imprinting in mammals: what a zoo!].
Proudhon, Charlotte; Bourc'his, Déborah
2010-05-01
Genomic imprinting imposes an obligate mode of biparental reproduction in mammals. This phenomenon results from the monoparental expression of a subset of genes. This specific gene regulation mechanism affects viviparous mammals, especially eutherians, but also marsupials to a lesser extent. Oviparous mammals, or monotremes, do not seem to demonstrate monoparental allele expression. This phylogenic confinement suggests that the evolution of the placenta imposed a selective pressure for the emergence of genomic imprinting. This physiological argument is now complemented by recent genomic evidence facilitated by the sequencing of the platypus genome, a rare modern day case of a monotreme. Analysis of the platypus genome in comparison to eutherian genomes shows a chronological and functional coincidence between the appearance of genomic imprinting and transposable element accumulation. The systematic comparative analyses of genomic sequences in different species is essential for the further understanding of genomic imprinting emergence and divergent evolution along mammalian speciation.
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
NASA Astrophysics Data System (ADS)
Hu, Dianyin; Gao, Ye; Meng, Fanchao; Song, Jun; Wang, Rongqiao
2018-04-01
Combining experiments and finite element analysis (FEA), a systematic study was performed to analyze the microstructural evolution and stress states of shot-peened GH4169 superalloy over a variety of peening intensities and coverages. A dislocation density evolution model was integrated into the representative volume FEA model to quantitatively predict microstructural evolution in the surface layers and compared with experimental results. It was found that surface roughness and through-depth residual stress profile are more sensitive to shot-peening intensity compared to coverage due to the high kinetic energy involved. Moreover, a surface nanocrystallization layer was discovered in the top surface region of GH4169 for all shot-peening conditions. However, the grain refinement was more intensified under high shot-peening coverage, under which enough time was permitted for grain refinement. The grain size gradient predicted by the numerical framework showed good agreement with experimental observations.
Coll-de-Tuero, Gabriel; González-Vázquez, Sonia; Rodríguez-Poncelas, Antonio; Barceló, María Antònia; Barrot-de-la Puente, Joan; Penedo, Manuel G; Pose-Reino, Antonio; Pena-Seijo, Marta; Saez, Marc
2014-02-01
There is no agreement on the systematic exploration of the fundus oculi (FO) in hypertensive patients, and it is unknown whether the evolution of retinal microcirculatory alterations has prognostic value or not. The aim of this study was to investigate whether the evolution of the arteriole-to-venule ratio (AVR) in newly-diagnosed hypertensive patients is associated with better or worse evolution of target organ damage (TOD) during 1 year. A cohort of 133 patients with newly-diagnosed untreated hypertension was followed for 1 year. At baseline and follow-up, all patients underwent a physical examination, self-blood pressure measurement, ambulatory blood pressure monitoring, blood and urine analysis, electrocardiogram, and retinography. The endpoint was the favourable evolution of TOD and the total amount of TOD, according to the baseline AVR and the baseline and final difference of the AVR. A total of 133 patients were analyzed (mean age, 57 ± 10.7 years; 59% men). No differences were found in the decrease in blood pressure or antihypertensive treatment between quartiles of baseline AVR or baseline-final AVR difference. Patients with a difference between baseline and final AVR in the highest quartile (>0.0817) had a favorable evolution of left ventricular hypertrophy (odds ratio, 14.9; 95% confidence interval, 1.08-206.8) and the amount of TOD (odds ratio, 2.22; 95% confidence interval, 1.03-6.05). No favorable evolution was found of glomerular filtration rate. There is an association between the evolution of the AVR and the favorable evolution of TOD. Patients with greater increase of AVR have significantly better evolution of left ventricular hypertrophy and amount of TOD. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.
A DNA Aptamer Recognizes the Asp f 1 Allergen of Aspergillus fumigatus
Low, Swee Yang; Hill, Jane E.; Peccia, Jordan
2009-01-01
Allergies are caused by the binding of IgE antibodies onto specific sites on allergens. However, in the assessment of exposure to airborne allergens, current techniques such as whole spore counts fail to account for the presence of these allergenic epitopes that trigger allergic reactions. The objective of the research is to develop a DNA aptamer for the Asp f 1 allergen of the pathogenic fungus Aspergillus fumigatus, using an IgE-binding epitope of the allergen as the target for aptamer selection. Through in vitro SELEX, an aptamer has been produced that binds with nanomolar affinity to the Asp f 1 IgE-epitope. The aptamer is also able to recognize the native Asp f 1 allergen, and does not bind to allergenic proteins from non-target mold species such as Alternaria alternata. Production of this aptamer provides proof-of-principle that allergen measurement methods can be developed to indicate the potent fraction, or allergenicity, of allergens. PMID:19545545
Preliminary Results of 3D-DDTC Pixel Detectors for the ATLAS Upgrade
DOE Office of Scientific and Technical Information (OSTI.GOV)
La Rosa, Alessandro; /CERN; Boscardin, M.
2012-04-04
3D Silicon sensors fabricated at FBK-irst with the Double-side Double Type Column (DDTC) approach and columnar electrodes only partially etched through p-type substrates were tested in laboratory and in a 1.35 Tesla magnetic field with a 180 GeV pion beam at CERN SPS. The substrate thickness of the sensors is about 200 {mu}m, and different column depths are available, with overlaps between junction columns (etched from the front side) and ohmic columns (etched from the back side) in the range from 110 {mu}m to 150 {mu}m. The devices under test were bump bonded to the ATLAS Pixel readout chip (FEI3)more » at SELEX SI (Rome, Italy). We report leakage current and noise measurements, results of functional tests with Am{sup 241} {gamma}-ray sources, charge collection tests with Sr90 {beta}-source and an overview of preliminary results from the CERN beam test.« less
Förster, Charlotte; Brauer, Arnd B. E.; Brode, Svenja; Schmidt, Kathrin S.; Perbandt, Markus; Meyer, Arne; Rypniewski, Wojciech; Betzel, Christian; Kurreck, Jens; Fürste, Jens P.; Erdmann, Volker A.
2006-01-01
The pharmacokinetic properties of an aptamer against the tumour-marker protein tenascin-C have recently been successfully improved by the introduction of locked nucleic acids (LNAs) into the terminal stem of the aptamer. Since it is believed that this post-SELEX optimization is likely to provide a more general route to enhance the in vitro and in vivo stability of aptamers, elucidation of the structural basis of this improvement was embarked upon. Here, the crystallographic and X-ray diffraction data of the isolated aptamer stem encompassed in a six-base-pair duplex both with and without the LNA modification are presented. The obtained all-LNA crystals belong to space group P41212 or P43212, with unit-cell parameters a = b = 52.80, c = 62.83 Å; the all-RNA crystals belong to space group R32, with unit-cell parameters a = b = 45.21, c = 186.97 Å, γ = 120.00°. PMID:16820689
Infrared engineering for the advancement of science: A UK perspective
NASA Astrophysics Data System (ADS)
Baker, Ian M.
2017-02-01
Leonardo MW (formerly Selex ES) has been developing infrared sensors and cameras for over 62 years at two main sites at Southampton and Basildon. Funding mainly from UK MOD has seen the technology progress from single element PbSe sensors to advanced, high definition, HgCdTe cameras, widely deployed in many fields today. However, in the last 10 years the major challenges and research funding has come from projects within the scientific sphere, particularly: astronomy and space. Low photon flux, high resolution spectroscopy and fast frame rates are the motivation to drive the sensitivity of infrared detectors to the single photon level. These detectors make use of almost noiseless avalanche gain in HgCdTe to achieve the sensitivity and speed of response. Metal Organic Vapour Phase Epitaxy, MOVPE, grown on low-cost GaAs substrates, provides the capability for crucial bandgap engineering to suppress breakdown currents and allow high avalanche gain even in very low background conditions. This paper describes the progress so far and provides a glimpse of the future.
Ultra compact spectrometer using linear variable filters
NASA Astrophysics Data System (ADS)
Dami, M.; De Vidi, R.; Aroldi, G.; Belli, F.; Chicarella, L.; Piegari, A.; Sytchkova, A.; Bulir, J.; Lemarquis, F.; Lequime, M.; Abel Tibérini, L.; Harnisch, B.
2017-11-01
The Linearly Variable Filters (LVF) are complex optical devices that, integrated in a CCD, can realize a "single chip spectrometer". In the framework of an ESA Study, a team of industries and institutes led by SELEX-Galileo explored the design principles and manufacturing techniques, realizing and characterizing LVF samples based both on All-Dielectric (AD) and Metal-Dielectric (MD) Coating Structures in the VNIR and SWIR spectral ranges. In particular the achieved performances on spectral gradient, transmission bandwidth and Spectral Attenuation (SA) are presented and critically discussed. Potential improvements will be highlighted. In addition the results of a feasibility study of a SWIR Linear Variable Filter are presented with the comparison of design prediction and measured performances. Finally criticalities related to the filter-CCD packaging are discussed. The main achievements reached during these activities have been: - to evaluate by design, manufacturing and test of LVF samples the achievable performances compared with target requirements; - to evaluate the reliability of the projects by analyzing their repeatability; - to define suitable measurement methodologies
U-Th-Pb, Sm-Nd, Rb-Sr, and Lu-Hf systematics of returned Mars samples
NASA Technical Reports Server (NTRS)
Tatsumoto, M.; Premo, W. R.
1988-01-01
The advantage of studying returned planetary samples cannot be overstated. A wider range of analytical techniques with higher sensitivities and accuracies can be applied to returned samples. Measurement of U-Th-Pb, Sm-Nd, Rb-Sr, and Lu-Hf isotopic systematics for chronology and isotopic tracer studies of planetary specimens cannot be done in situ with desirable precision. Returned Mars samples will be examined using all the physical, chemical, and geologic methods necessary to gain information on the origin and evolution of Mars. A returned Martian sample would provide ample information regarding the accretionary and evolutionary history of the Martian planetary body and possibly other planets of our solar system.
Cushion, Christopher; Harvey, Stephen; Muir, Bob; Nelson, Lee
2012-01-01
We outline the evolution of a computerised systematic observation tool and describe the process for establishing the validity and reliability of this new instrument. The Coach Analysis and Interventions System (CAIS) has 23 primary behaviours related to physical behaviour, feedback/reinforcement, instruction, verbal/non-verbal, questioning and management. The instrument also analyses secondary coach behaviour related to performance states, recipient, timing, content and questioning/silence. The CAIS is a multi-dimensional and multi-level mechanism able to provide detailed and contextualised data about specific coaching behaviours occurring in complex and nuanced coaching interventions and environments that can be applied to both practice sessions and competition.
On the Overdispersed Molecular Clock
Takahata, Naoyuki
1987-01-01
Rates of molecular evolution at some loci are more irregular than described by simple Poisson processes. Three situations under which molecular evolution would not follow simple Poisson processes are reevaluated from the viewpoint of the neutrality hypothesis: (i) concomitant or multiple substitutions in a gene, (ii) fluctuating substitution rates in time caused by coupled effects of deleterious mutations and bottlenecks, and (iii) changes in the degree of selective constraints against a gene (neutral space) caused by successive substitutions. The common underlying assumption that these causes are lineage nonspecific excludes the case where mutation rates themselves change systematically among lineages or taxonomic groups, and severely limits the extent of variation in the number of substitutions among lineages. Even under this stringent condition, however, the third hypothesis, the fluctuating neutral space model, can generate fairly large variation. This is described by a time-dependent renewal process, which does not exhibit any episodic nature of molecular evolution. It is argued that the observed elevated variances in the number of nucleotide or amino acid substitutions do not immediately call for positive Darwinian selection in molecular evolution. PMID:3596230
Antigenic Patterns and Evolution of the Human Influenza A (H1N1) Virus
Liu, Mi; Zhao, Xiang; Hua, Sha; Du, Xiangjun; Peng, Yousong; Li, Xiyan; Lan, Yu; Wang, Dayan; Wu, Aiping; Shu, Yuelong; Jiang, Taijiao
2015-01-01
The influenza A (H1N1) virus causes seasonal epidemics that result in severe illnesses and deaths almost every year. A deep understanding of the antigenic patterns and evolution of human influenza A (H1N1) virus is extremely important for its effective surveillance and prevention. Through development of antigenicity inference method for human influenza A (H1N1), named PREDAC-H1, we systematically mapped the antigenic patterns and evolution of the human influenza A (H1N1) virus. Eight dominant antigenic clusters have been inferred for seasonal H1N1 viruses since 1977, which demonstrated sequential replacements over time with a similar pattern in Asia, Europe and North America. Among them, six clusters emerged first in Asia. As for China, three of the eight antigenic clusters were detected in South China earlier than in North China, indicating the leading role of South China in H1N1 transmission. The comprehensive view of the antigenic evolution of human influenza A (H1N1) virus can help formulate better strategy for its prevention and control. PMID:26412348
Antigenic Patterns and Evolution of the Human Influenza A (H1N1) Virus.
Liu, Mi; Zhao, Xiang; Hua, Sha; Du, Xiangjun; Peng, Yousong; Li, Xiyan; Lan, Yu; Wang, Dayan; Wu, Aiping; Shu, Yuelong; Jiang, Taijiao
2015-09-28
The influenza A (H1N1) virus causes seasonal epidemics that result in severe illnesses and deaths almost every year. A deep understanding of the antigenic patterns and evolution of human influenza A (H1N1) virus is extremely important for its effective surveillance and prevention. Through development of antigenicity inference method for human influenza A (H1N1), named PREDAC-H1, we systematically mapped the antigenic patterns and evolution of the human influenza A (H1N1) virus. Eight dominant antigenic clusters have been inferred for seasonal H1N1 viruses since 1977, which demonstrated sequential replacements over time with a similar pattern in Asia, Europe and North America. Among them, six clusters emerged first in Asia. As for China, three of the eight antigenic clusters were detected in South China earlier than in North China, indicating the leading role of South China in H1N1 transmission. The comprehensive view of the antigenic evolution of human influenza A (H1N1) virus can help formulate better strategy for its prevention and control.
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
Grismer, L Lee; Wood, P L Jr; Tri, Ngo Van; Murdoch, Matthew L
2015-06-26
An integrative taxonomic analysis of the distantly related Cyrtodactylus condorensis and intermedius species complexes of the Mekong Delta revealed that C. paradoxus is a junior synonym of C. condorensis and that C. thochuensis is a junior synonym of C. leegrismeri. Additionally, the analysis revealed that a cave-dwelling ecomorpholgy has evolved independently early on in the evolution of both complexes (represented by C. hontreensis in the intermedius complex and C. grismeri and C. eisenmani in the condorensis complex) and cave ecomorphs exist in sympatry-but not syntopy-with general scansorial ecomorphs. Multiple, recent, cyclical, glacioeustatic driven changes in sea levels across the Sunda Shelf are hypothesized to account for the evolution and distribution of the widely separated, conspecific insular populations of C. condorensis and C. leegrismeri. The independent evolution of cave ecomorphology is proposed to have been driven by competition avoidance. Habitat islands across the Mekong Delta are an important source of endemism and in need of protection.
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…
Hyb-Seq: combining target enrichment and genome skimming for plant phylogenomics
Kevin Weitemier; Shannon C.K. Straub; Richard C. Cronn; Mark Fishbein; Roswitha Schmickl; Angela McDonnell; Aaron Liston
2014-01-01
⢠Premise of the study: Hyb-Seq, the combination of target enrichment and genome skimming, allows simultaneous data collection for low-copy nuclear genes and high-copy genomic targets for plant systematics and evolution studies. ⢠Methods and Results: Genome and transcriptome assemblies for milkweed ( Asclepias syriaca ) were used to design enrichment probes for 3385...
ERIC Educational Resources Information Center
Villani, Alberto; Dias, Valeria Silva; Valadares, Juarez Melgaco
2010-01-01
Over the last 50 years a new research area, science education research, has arisen and undergone singular development worldwide. In the specific case of Brazil, research in science education first appeared systematically 40 years ago, as a consequence of an overall renovation in the field of science education. This evolution was also related to…
USDA-ARS?s Scientific Manuscript database
The predominantly holarctic bee genus Osmia is species-rich and behaviorally diverse. A robust phylogeny of this genus is important for understanding the evolution of the immense variety of morphological and behavioral traits exhibited by this group. We infer a phylogeny of Osmia using DNA sequenc...
A Time Line of the Evolution of School Bullying in Differing Social Contexts
ERIC Educational Resources Information Center
Koo, Hyojin
2007-01-01
The aim of this present study is to expand our general understanding of bullying behaviour and to advance our knowledge about bullying among pupils. As evidenced by historical documents, the phenomenon of bullying is not a new concept. The fact that some people are frequently and systematically harassed or attacked by others is described in…
Investigation of the particle-core structure of odd-mass nuclei in the NpNn scheme
NASA Astrophysics Data System (ADS)
Bucurescu, D.; Cata, G.; Cutoiu, D.; Dragulescu, E.; Ivasu, M.; Zamfir, N. V.; Gizon, A.; Gizon, J.
1989-10-01
The NpNn scheme is applied to data related to collective band structures determined by the unique parity shell model orbitals in odd-A nuclei from the mass regions A≌80-100 and A≌130. Simple systematics are obtained which give a synthetic picture of the evolution of the particle-core coupling in these nuclear regions.
NASA Astrophysics Data System (ADS)
Gao, Cheng; Zeng, Jiaolong; Yuan, Jianmin
2015-11-01
Emissivity of single core-hole (SCH) and double core-hole (DCH) states of aluminum plasmas produced in the interaction with ultra-intense x-ray laser pulse interaction are investigated systematically by solving the time-dependent rate equation implemented in the detailed level accounting approximation. We first demonstrated the plasma density effects on level populations and charge state distribution. Compared with recent experiments, it is shown that the plasma density effects play important roles in the evolution dynamics. Then we systematically investigated the emissivity of the transient aluminum plasmas produced by the x-ray laser pulses with a few photon energies above the threshold photon energy to create DCH states. For the laser photon energy where there are resonant absorptions (RA), 1s-np transitions with both full 1s and SCH 1s states play important roles in time evolution of the population and DCH emission spectroscopy. The significant RA effects are illustrated in detail for x-ray pulses, which creates the 1s-2p resonant absorption from the SCH states of Al VII. With the increase of the photon energy, the emissions from lower charge states become larger.
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.
CI as a Tracer of Gas Mass in Star Forming Galaxies
NASA Astrophysics Data System (ADS)
Bourne, Nathan
2018-01-01
Research in galaxy evolution aims to understand the cosmic industry of converting gas into stars. While SFR and stellar mass evolution are well constrained by current data, our knowledge of gas in galaxies throughout cosmic time is comparatively lacking. Almost all high-redshift gas measurements to date rely on CO as a tracer, but this is subject to systematic uncertainties due to optically thick emission and poorly constrained dependences on gas density, distribution and metallicity. Recently, some attention has been given to dust continuum as an alternative gas tracer, which shows promise for large samples but still requires accurate calibration on a direct gas tracer at high redshift. The [CI] 492GHz emission line could overcome much of the systematic uncertainty, as it is optically thin and has similar excitation conditions to CO(1-0), but observational limitations have so far restricted CI measurements to very small samples. I will presen t some new data from ALMA, for the first time testing the CI/dust correlation in a representative sample of star-forming galaxies at z=1, and discuss how future observations could be designed to more widely exploit this independent gas tracer.
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.
Combining states without scale hierarchies with ordered parton showers
Fischer, Nadine; Prestel, Stefan
2017-09-12
Here, we present a parameter-free scheme to combine fixed-order multi-jet results with parton-shower evolution. The scheme produces jet cross sections with leading-order accuracy in the complete phase space of multiple emissions, resumming large logarithms when appropriate, while not arbitrarily enforcing ordering on momentum configurations beyond the reach of the parton-shower evolution equation. This then requires the development of a matrix-element correction scheme for complex phase-spaces including ordering conditions as well as a systematic scale-setting procedure for unordered phase-space points. Our algorithm does not require a merging-scale parameter. We implement the new method in the Vincia framework and compare to LHCmore » data.« less
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.
A Comparison of Three Elliptical Galaxy Photochemical Evolution Codes
NASA Astrophysics Data System (ADS)
Gibson, Brad K.
1996-09-01
Working within the classic supernovae-driven wind framework for elliptical galaxy evolution, We perform a systematic investigation into the discrepancies between the predictions of three contemporary codes (by Arimoto & Yoshii, Bressan et al., and Gibson). By being primarily concerned with reproducing the present-day color-metallicity-luminosity (CML) relations among elliptical galaxies, the approaches taken in the theoretical modeling have managed to obscure many of the hidden differences between the codes. Targeting the timescale for the onset of the initial galactic wind, t_GW_, as a primary "difference" indicator, We demonstrate exactly how and why each code is able to claim successful reproduction of the CML relations, despite possessing apparently incompatible input ingredients.
The nature, origin and evolution of embedded star clusters
NASA Technical Reports Server (NTRS)
Lada, Charles J.; Lada, Elizabeth A.
1991-01-01
The recent development of imaging infrared array cameras has enabled the first systematic studies of embedded protoclusters in the galaxy. Initial investigations suggest that rich embedded clusters are quite numerous and that a significant fraction of all stars formed in the galaxy may begin their lives in such stellar systems. These clusters contain extremely young stellar objects and are important laboratories for star formation research. However, observational and theoretical considerations suggest that most embedded clusters do not survive emergence from molecular clouds as bound clusters. Understanding the origin, nature, and evolution of embedded clusters requires understanding the intimate physical relation between embedded clusters and the dense molecular cloud cores from which they form.
Hutton, Brian; Salanti, Georgia; Caldwell, Deborah M; Chaimani, Anna; Schmid, Christopher H; Cameron, Chris; Ioannidis, John P A; Straus, Sharon; Thorlund, Kristian; Jansen, Jeroen P; Mulrow, Cynthia; Catalá-López, Ferrán; Gøtzsche, Peter C; Dickersin, Kay; Boutron, Isabelle; Altman, Douglas G; Moher, David
2015-06-02
The PRISMA statement is a reporting guideline designed to improve the completeness of reporting of systematic reviews and meta-analyses. Authors have used this guideline worldwide to prepare their reviews for publication. In the past, these reports typically compared 2 treatment alternatives. With the evolution of systematic reviews that compare multiple treatments, some of them only indirectly, authors face novel challenges for conducting and reporting their reviews. This extension of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement was developed specifically to improve the reporting of systematic reviews incorporating network meta-analyses. A group of experts participated in a systematic review, Delphi survey, and face-to-face discussion and consensus meeting to establish new checklist items for this extension statement. Current PRISMA items were also clarified. A modified, 32-item PRISMA extension checklist was developed to address what the group considered to be immediately relevant to the reporting of network meta-analyses. This document presents the extension and provides examples of good reporting, as well as elaborations regarding the rationale for new checklist items and the modification of previously existing items from the PRISMA statement. It also highlights educational information related to key considerations in the practice of network meta-analysis. The target audience includes authors and readers of network meta-analyses, as well as journal editors and peer reviewers.
A Study of Pulse Shape Evolution and X-Ray Reprocessing in Her X-1
NASA Technical Reports Server (NTRS)
Cushman, Paula P.
1998-01-01
This study focused on the pulse shape evolution and spectral properties of the X-ray binary Her X-1 with regard to the well known 35-day cycle of Her X-1. A follow-up set of RXTE observations has been conducted in RXTE AO-2 phase and the two observation sets are being analyzed together. We presented results of early analysis of pulse shape evolution in "Proceedings of the Fourth Compton Symposium". More advanced analysis was presented at the HEAD meeting in November, 1997 in Estes Park, Colorado. A related study of the 35-day cycle using RXTE/ASM data, which laid out the overall picture within which the more detailed PCA observations could be placed has also been conducted. The results of this study have been published. A pair of papers on the detailed pulse evolution and the spectral/color evolution are currently being prepared for publication. Some of the significant results of this study have been a confirmation of the detailed pulse profile changes at the end of the Main High state in HerX-1 first observed by GINGA, observations of the pulse evolution in several Short High states which agree with the pulse evolution pattern predicted using a disk occultation model, observation of a systematic lengthening of the eclipse egress during the Main High state of the 35-day phase and observation of a new type of extended eclipse ingress during which pulsations cease to observed during the Short High state.
Nelson, Craig E
2008-08-01
The strength of the evidence supporting evolution has increased markedly since the discovery of DNA but, paradoxically, public resistance to accepting evolution seems to have become stronger. A key dilemma is that science faculty have often continued to teach evolution ineffectively, even as the evidence that traditional ways of teaching are inferior has become stronger and stronger. Three pedagogical strategies that together can make a large difference in students' understanding and acceptance of evolution are extensive use of interactive engagement, a focus on critical thinking in science (especially on comparisons and explicit criteria) and using both of these in helping the students actively compare their initial conceptions (and publicly popular misconceptions) with more fully scientific conceptions. The conclusion that students' misconceptions must be dealt with systematically can be difficult for faculty who are teaching evolution since much of the students' resistance is framed in religious terms and one might be reluctant to address religious ideas in class. Applications to teaching evolution are illustrated with examples that address criteria and critical thinking, standard geology versus flood geology, evolutionary developmental biology versus organs of extreme perfection, and the importance of using humans as a central example. It is also helpful to bridge the false dichotomy, seen by many students, between atheistic evolution versus religious creationism. These applications are developed in detail and are intended to be sufficient to allow others to use these approaches in their teaching. Students and other faculty were quite supportive of these approaches as implemented in my classes.
Lonjon, Guillaume; Porcher, Raphael; Ergina, Patrick; Fouet, Mathilde; Boutron, Isabelle
2017-05-01
To describe the evolution of the use and reporting of propensity score (PS) analysis in observational studies assessing a surgical procedure. Assessing surgery in randomized controlled trials raises several challenges. Observational studies with PS analysis are a robust alternative for comparative effectiveness research. In this methodological systematic review, we identified all PubMed reports of observational studies with PS analysis that evaluated a surgical procedure and described the evolution of their use over time. Then, we selected a sample of articles published from August 2013 to July 2014 and systematically appraised the quality of reporting and potential bias of the PS analysis used. We selected 652 reports of observational studies with PS analysis. The publications increased over time, from 1 report in 1987 to 198 in 2013. Among the 129 reports assessed, 20% (n = 24) did not detail the covariates included in the PS and 77% (n = 100) did not report a justification for including these covariates in the PS. The rate of missing data for potential covariates was reported in 9% of articles. When a crossover by conversion was possible, only 14% of reports (n = 12) mentioned this issue. For matched analysis, 10% of articles reported all 4 key elements that allow for reproducibility of a PS-matched analysis (matching ratio, method to choose the nearest neighbors, replacement and method for statistical analysis). Observational studies with PS analysis in surgery are increasing in frequency, but specific methodological issues and weaknesses in reporting exist.
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.
Fortin, Connor H; Schulze, Katharina V; Babbitt, Gregory A
2015-01-01
It is now widely-accepted that DNA sequences defining DNA-protein interactions functionally depend upon local biophysical features of DNA backbone that are important in defining sites of binding interaction in the genome (e.g. DNA shape, charge and intrinsic dynamics). However, these physical features of DNA polymer are not directly apparent when analyzing and viewing Shannon information content calculated at single nucleobases in a traditional sequence logo plot. Thus, sequence logos plots are severely limited in that they convey no explicit information regarding the structural dynamics of DNA backbone, a feature often critical to binding specificity. We present TRX-LOGOS, an R software package and Perl wrapper code that interfaces the JASPAR database for computational regulatory genomics. TRX-LOGOS extends the traditional sequence logo plot to include Shannon information content calculated with regard to the dinucleotide-based BI-BII conformation shifts in phosphate linkages on the DNA backbone, thereby adding a visual measure of intrinsic DNA flexibility that can be critical for many DNA-protein interactions. TRX-LOGOS is available as an R graphics module offered at both SourceForge and as a download supplement at this journal. To demonstrate the general utility of TRX logo plots, we first calculated the information content for 416 Saccharomyces cerevisiae transcription factor binding sites functionally confirmed in the Yeastract database and matched to previously published yeast genomic alignments. We discovered that flanking regions contain significantly elevated information content at phosphate linkages than can be observed at nucleobases. We also examined broader transcription factor classifications defined by the JASPAR database, and discovered that many general signatures of transcription factor binding are locally more information rich at the level of DNA backbone dynamics than nucleobase sequence. We used TRX-logos in combination with MEGA 6.0 software for molecular evolutionary genetics analysis to visually compare the human Forkhead box/FOX protein evolution to its binding site evolution. We also compared the DNA binding signatures of human TP53 tumor suppressor determined by two different laboratory methods (SELEX and ChIP-seq). Further analysis of the entire yeast genome, center aligned at the start codon, also revealed a distinct sequence-independent 3 bp periodic pattern in information content, present only in coding region, and perhaps indicative of the non-random organization of the genetic code. TRX-LOGOS is useful in any situation in which important information content in DNA can be better visualized at the positions of phosphate linkages (i.e. dinucleotides) where the dynamic properties of the DNA backbone functions to facilitate DNA-protein interaction.
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.
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.
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.
Ekpyrosis and inflationary dynamics in heavy ion collisions: the role of quantum fluctuations
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dusling, K.; Venugopalan, R.; Gelis, F.
We summarize recent significant progress in the development of a first-principles formalism to describe the formation and evolution of matter in very high energy heavy ion collisions. The key role of quantum fluctuations both before and after a collision is emphasized. Systematic computations are now feasible to address early time isotropization, flow, parton energy loss and the Chiral Magnetic Effect.
ERIC Educational Resources Information Center
Wallace, Colin S.
2011-01-01
This study reports the results of the first systematic investigation into Astro 101 students' conceptual and reasoning difficulties with cosmology. We developed four surveys with which we measured students' conceptual knowledge of the Big Bang, the expansion and evolution of the universe, and the evidence for dark matter. Our classical test theory…
NASA Astrophysics Data System (ADS)
van der Marel, Roeland P.; van Dokkum, Pieter G.
2007-10-01
We study the mass-to-light ratio (M/L) evolution of early-type galaxies using dynamical modeling of resolved internal kinematics. This makes fewer assumptions than fundamental plane (FP) studies and provides a powerful new approach for studying galaxy evolution. We focus on the sample of 25 galaxies in clusters at z~0.5 modeled in Paper I. For comparison, we compile and homogenize M/L literature data for 60 nearby galaxies that were modeled in comparable detail. The nearby sample obeys log(M/L)B=Z+Slog(σeff/200 km s-1), where Z=0.896+/-0.010, S=0.992+/-0.054, and σeff is the effective velocity dispersion. The z~0.5 sample follows a similar relation, but with lower zero point. The implied M/L evolution is Δlog(M/L)/Δz=-0.457+/-0.046(random)+/-0.078(systematic), consistent with passive evolution following high-redshift formation. This agrees with the FP results for this sample by van Dokkum & van der Marel, and confirms that FP evolution tracks M/L evolution, which is an important verification of the assumptions that underlie FP studies. However, while we find more FP evolution for galaxies of low σeff (or low mass), the dynamical M/L evolution shows little correlation with σeff. We argue that this difference can be plausibly attributed to a combination of two effects: (1) evolution in structural galaxy properties other than M/L, and (2) the neglect of rotational support in studies of FP evolution. The results leave the question open as to whether the low-mass galaxies in the sample have younger populations than the high-mass galaxies. This highlights the general importance in the study of population ages for complementing dynamical measurements with broadband colors or spectroscopic population diagnostics.
Lu-Hf CONSTRAINTS ON THE EVOLUTION OF LUNAR BASALTS.
Fujimaki, Hirokazu; Tatsumoto, Mistunobu
1984-01-01
The authors show that a cumulate-remelting model best explains the recently acquired data on the Lu-Hf systematics of lunar mare basalts. The authors model is first constructed using the Lu and Hf concentration data and it is then further strengthened by the Hf isotopic evidence. The authors also show that the similarity of MgO/FeO ratios and the Cr//2O//3 contents between high-Ti and low-Ti basalts, which have been given significance by A. E. Ringwood and D. H. Green are not important constraints for lunar basalt petrogenesis. The authors principal aim is to revive the remelting model for further consideration with the powerful constraints of Lu-Hf systematics of lunar basalts.
Os isotopes in SNC meteorites and their implications to the early evolution of Mars and Earth
NASA Technical Reports Server (NTRS)
Jagoutz, E.; Luck, J. M.; Othman, D. Ben; Wanke, H.
1993-01-01
A new development on the measurement of the Os isotopic composition by mass spectrometry using negative ions opened a new field of applications. The Re-Os systematic provides time information on the differentiation of the nobel metals. The nobel metals are strongly partitioned into metal and sulphide phases, but also the generation of silicate melts might fractionate the Re-Os system. Compared to the other isotopic systems which are mainly dating the fractionation of the alkalis and alkali-earth elements, the Re-Os system is expected to disclose entirely new information about the geochemistry. Especially the differentiation and early evolution of the planets such as the formation of the core will be elucidated with this method.
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.
The evolution of Internet addiction: A global perspective.
Griffiths, Mark D; Kuss, Daria J; Billieux, Joël; Pontes, Halley M
2016-02-01
Kimberly Young's initial work on Internet addiction (IA) was pioneering and her early writings on the topic inspired many others to carry out research in the area. Young's (2015) recent paper on the 'evolution of Internet addiction' featured very little European research, and did not consider the main international evidence that has contributed to our current knowledge about the conceptualization, epidemiology, etiology, and course of Internet-related disorders. This short commentary paper elaborates on important literature omitted by Young that the present authors believe may be of use to researchers. We also address statements made in Young's (2015) commentary that are incorrect (and therefore misleading) and not systematically substantiated by empirical evidence. Copyright © 2015 Elsevier Ltd. All rights reserved.
Calibration of Herschel SPIRE FTS observations at different spectral resolutions
NASA Astrophysics Data System (ADS)
Marchili, N.; Hopwood, R.; Fulton, T.; Polehampton, E. T.; Valtchanov, I.; Zaretski, J.; Naylor, D. A.; Griffin, M. J.; Imhof, P.; Lim, T.; Lu, N.; Makiwa, G.; Pearson, C.; Spencer, L.
2017-01-01
The SPIRE Fourier Transform Spectrometer on-board the Herschel Space Observatory had two standard spectral resolution modes for science observations: high resolution (HR) and low resolution (LR), which could also be performed in sequence (H+LR). A comparison of the HR and LR resolution spectra taken in this sequential mode revealed a systematic discrepancy in the continuum level. Analysing the data at different stages during standard pipeline processing demonstrates that the telescope and instrument emission affect HR and H+LR observations in a systematically different way. The origin of this difference is found to lie in the variation of both the telescope and instrument response functions, while it is triggered by fast variation of the instrument temperatures. As it is not possible to trace the evolution of the response functions using housekeeping data from the instrument subsystems, the calibration cannot be corrected analytically. Therefore, an empirical correction for LR spectra has been developed, which removes the systematic noise introduced by the variation of the response functions.
Functional Independent Scaling Relation for ORR/OER Catalysts
Christensen, Rune; Hansen, Heine A.; Dickens, Colin F.; ...
2016-10-11
A widely used adsorption energy scaling relation between OH* and OOH* intermediates in the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), has previously been determined using density functional theory and shown to dictate a minimum thermodynamic overpotential for both reactions. Here, we show that the oxygen–oxygen bond in the OOH* intermediate is, however, not well described with the previously used class of exchange-correlation functionals. By quantifying and correcting the systematic error, an improved description of gaseous peroxide species versus experimental data and a reduction in calculational uncertainty is obtained. For adsorbates, we find that the systematic error largelymore » cancels the vdW interaction missing in the original determination of the scaling relation. An improved scaling relation, which is fully independent of the applied exchange–correlation functional, is obtained and found to differ by 0.1 eV from the original. Lastly, this largely confirms that, although obtained with a method suffering from systematic errors, the previously obtained scaling relation is applicable for predictions of catalytic activity.« less
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.
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.
The role of the basic state in the ENSO-monsoon relationship and implications for predictability
NASA Astrophysics Data System (ADS)
Turner, A. G.; Inness, P. M.; Slingo, J. M.
2005-04-01
The impact of systematic model errors on a coupled simulation of the Asian summer monsoon and its interannual variability is studied. Although the mean monsoon climate is reasonably well captured, systematic errors in the equatorial Pacific mean that the monsoon-ENSO teleconnection is rather poorly represented in the general-circulation model. A system of ocean-surface heat flux adjustments is implemented in the tropical Pacific and Indian Oceans in order to reduce the systematic biases. In this version of the general-circulation model, the monsoon-ENSO teleconnection is better simulated, particularly the lag-lead relationships in which weak monsoons precede the peak of El Niño. In part this is related to changes in the characteristics of El Niño, which has a more realistic evolution in its developing phase. A stronger ENSO amplitude in the new model version also feeds back to further strengthen the teleconnection. These results have important implications for the use of coupled models for seasonal prediction of systems such as the monsoon, and suggest that some form of flux correction may have significant benefits where model systematic error compromises important teleconnections and modes of interannual variability.
Pulse Shape Evolution, HER X-1
NASA Technical Reports Server (NTRS)
VanParadijs, Johannes A.
1998-01-01
This study focuses on the pulse shape evolution and spectral properties of the X-ray binary Her X-1 with regard to the well known 35-day cycle of Her X-1. A follow-up set of RXTE observations has been conducted in RXTE AO-2 phase and the two observation sets are being analyzed together. We presented results of early analysis of pulse shape evolution in "Proceedings of the Fourth Compton Symposium." More advanced analysis was presented at the HEAD meeting in November, 1997 in Estes Park, Colorado. A related study of the 35-day cycle using RXTE/ASM data, which laid out the overall picture within which the more detailed PCA observations could be placed has also been conducted. The results of this study have been published in The Astrophysical Journal, vol. 510, 974. A pair of papers on the detailed pulse evolution and the spectral/color evolution are currently being prepared for publication. Some of the significant results of this study have been a confirmation of the detailed pulse profile changes at the end of the Main High state in Her X-1 first observed by GINGA, observations of the pulse evolution in several Short High states which agree with the pulse evolution pattern predicted using a disk occultation model in the PhD Thesis of Scott 1993, observation of a systematic lengthening of the eclipse egress during the Main High state of the 35-day phase and observation of a new type of extended eclipse ingress during which pulsations cease to observed during the Short High state.
NASA Astrophysics Data System (ADS)
Lv, Xiaowei; Xiao, Xin; Cao, Minglei; Bu, Yi; Wang, Chuanqing; Wang, Mingkui; Shen, Yan
2018-05-01
Modification of semiconductor photoanodes with oxygen evolution catalyst (OEC) is an effective approach for improving photoelectrochemical (PEC) water splitting efficiency. In the configuration, how to increase the activity of OEC is crucial to further improve PEC performance. Herein, a ternary photoanode system was designed to enhance PEC efficiency of photoelectrodes through introducing carbon dots (CDs), NiFe-layered double hydroxide (NiFe-LDH) nanosheets on BiVO4 particles. Systematic research shows that NiFe-LDH serves as an OEC which accelerates oxygen evolution kinetics, while the introduction of CDs can further reduce charge transfer resistance and overpotential for oxygen evolution. Under the synergistic effect of NiFe-LDH and CDs, the photocurrent and incident photon to current conversion efficiency (IPCE) of the resulting CDs/NiFe-LDH/BiVO4 photoanode is improved significantly than those of the NiFe-LDH/BiVO4 electrode. Consequently, such a ternary heterostructure could be an alternative way to further enhance PEC water splitting performance.
Protein interactions and ligand binding: from protein subfamilies to functional specificity.
Rausell, Antonio; Juan, David; Pazos, Florencio; Valencia, Alfonso
2010-02-02
The divergence accumulated during the evolution of protein families translates into their internal organization as subfamilies, and it is directly reflected in the characteristic patterns of differentially conserved residues. These specifically conserved positions in protein subfamilies are known as "specificity determining positions" (SDPs). Previous studies have limited their analysis to the study of the relationship between these positions and ligand-binding specificity, demonstrating significant yet limited predictive capacity. We have systematically extended this observation to include the role of differential protein interactions in the segregation of protein subfamilies and explored in detail the structural distribution of SDPs at protein interfaces. Our results show the extensive influence of protein interactions in the evolution of protein families and the widespread association of SDPs with protein interfaces. The combined analysis of SDPs in interfaces and ligand-binding sites provides a more complete picture of the organization of protein families, constituting the necessary framework for a large scale analysis of the evolution of protein function.
Spectral lags in different episodes of gamma-ray bursts
NASA Astrophysics Data System (ADS)
Jia, LanWei; Yi, TingFeng; Liang, EnWei
2013-08-01
A systematical analysis of the spectral lags in different episodes within a gamma-ray burst (GRB) for the BATSE GRB sample is given. The identified episodes are usually a single pulse with mixing of small fluctuations. The spectral lags were calculated for lightcurves in the 25-55 keV and 110-320 keV bands. No universal spectral lag evolution feature in different episodes within a GRB were found for most GRBs. Among 362 bright GRBs that have at least three well-identified episodes, 19 of them show long-to-short lag and 19 of them show short-to-long lag in successive episodes. The other 324 GRBs have no clear evolution trend. Defining the specified lag with the ratio of the spectral lag to the episode duration in 110-320 keV band, no prominent case of specified lag was found showing clear evolution features. The results suggest that the observed spectral lag may contribute to the dynamics and/or the radiation physics of a given emission episode.
Cross-cultural dataset for the evolution of religion and morality project.
Purzycki, Benjamin Grant; Apicella, Coren; Atkinson, Quentin D; Cohen, Emma; McNamara, Rita Anne; Willard, Aiyana K; Xygalatas, Dimitris; Norenzayan, Ara; Henrich, Joseph
2016-11-08
A considerable body of research cross-culturally examines the evolution of religious traditions, beliefs and behaviors. The bulk of this research, however, draws from coded qualitative ethnographies rather than from standardized methods specifically designed to measure religious beliefs and behaviors. Psychological data sets that examine religious thought and behavior in controlled conditions tend to be disproportionately sampled from student populations. Some cross-national databases employ standardized methods at the individual level, but are primarily focused on fully market integrated, state-level societies. The Evolution of Religion and Morality Project sought to generate a data set that systematically probed individual level measures sampling across a wider range of human populations. The set includes data from behavioral economic experiments and detailed surveys of demographics, religious beliefs and practices, material security, and intergroup perceptions. This paper describes the methods and variables, briefly introduces the sites and sampling techniques, notes inconsistencies across sites, and provides some basic reporting for the data set.
Cross-cultural dataset for the evolution of religion and morality project
Purzycki, Benjamin Grant; Apicella, Coren; Atkinson, Quentin D.; Cohen, Emma; McNamara, Rita Anne; Willard, Aiyana K.; Xygalatas, Dimitris; Norenzayan, Ara; Henrich, Joseph
2016-01-01
A considerable body of research cross-culturally examines the evolution of religious traditions, beliefs and behaviors. The bulk of this research, however, draws from coded qualitative ethnographies rather than from standardized methods specifically designed to measure religious beliefs and behaviors. Psychological data sets that examine religious thought and behavior in controlled conditions tend to be disproportionately sampled from student populations. Some cross-national databases employ standardized methods at the individual level, but are primarily focused on fully market integrated, state-level societies. The Evolution of Religion and Morality Project sought to generate a data set that systematically probed individual level measures sampling across a wider range of human populations. The set includes data from behavioral economic experiments and detailed surveys of demographics, religious beliefs and practices, material security, and intergroup perceptions. This paper describes the methods and variables, briefly introduces the sites and sampling techniques, notes inconsistencies across sites, and provides some basic reporting for the data set. PMID:27824332
A Framework for Intentional Cultural Change
Biglan, Anthony; Embry, Dennis D.
2013-01-01
We present a framework for a pragmatic science of cultural evolution. It is now possible for behavioral science to systematically influence the further evolution of cultural practices. As this science develops, it may become possible to prevent many of the problems affecting human wellbeing. By cultural practices, we refer to everything that humans do, above and beyond instinctual or unconditioned behaviors: not only art and literature, but also agriculture, manufacturing, recreation, war making, childrearing, science—everything. We can analyze cultural practices usefully in terms of the incidence and prevalence of individual behavior and group and organization actions. An effective science of intentional cultural evolution must guide efforts to influence the incidence and prevalence of individuals’ behaviors and the actions of groups and organizations. In this paper, we briefly sketch advances in scientific understanding of the influences on individual behavior. Then we describe principles that could guide efforts to influence groups and organizations. Finally, we discuss legitimate concerns about the use and misuse of a science for intentional cultural change. PMID:24363988
PHYSICS OF NON-GAUSSIAN FIELDS AND THE COSMOLOGICAL GENUS STATISTIC
DOE Office of Scientific and Technical Information (OSTI.GOV)
James, J. Berian, E-mail: berian@berkeley.edu
2012-05-20
We report a technique to calculate the impact of distinct physical processes inducing non-Gaussianity on the cosmological density field. A natural decomposition of the cosmic genus statistic into an orthogonal polynomial sequence allows complete expression of the scale-dependent evolution of the topology of large-scale structure, in which effects including galaxy bias, nonlinear gravitational evolution, and primordial non-Gaussianity may be delineated. The relationship of this decomposition to previous methods for analyzing the genus statistic is briefly considered and the following applications are made: (1) the expression of certain systematics affecting topological measurements, (2) the quantification of broad deformations from Gaussianity thatmore » appear in the genus statistic as measured in the Horizon Run simulation, and (3) the study of the evolution of the genus curve for simulations with primordial non-Gaussianity. These advances improve the treatment of flux-limited galaxy catalogs for use with this measurement and further the use of the genus statistic as a tool for exploring non-Gaussianity.« less
A large Cretaceous theropod from Patagonia, Argentina, and the evolution of carcharodontosaurids.
Novas, Fernando E; de Valais, Silvina; Vickers-Rich, Pat; Rich, Tom
2005-05-01
The Cretaceous Carcharodontosauridae is the latest clade of carnosaurs, including the largest predatory dinosaurs yet recorded. Albeit spectacular for their size, the skeletal anatomy of these theropods remains poorly-known, and their diversity was until recently restricted to two Cenomanian species: the highly derived Giganotosaurus carolinii, from southern South America, and the incompletely known Carcharodontosaurus saharicus, from northern Africa. Here we describe an older and basal member of the group, Tyrannotitan chubutensis gen. et sp. nov., from Aptian strata of Patagonia, Argentina. The new taxon gives new insights into the systematics and evolution of carcharodontosaurids and offers a better understanding of the evolution of Southern theropod faunas. We suggest that carcharodontosaurids radiated in Gondwana sharing with spinosaurids the role of top-predators until their extinction in Cenomanian-Turonian times. During this interval, the diplodocoid sauropods and giant titanosaurians went extinct (probably as part of a global-scale crisis), and the smaller abelisaurid theropods took dominance, reigning until the end of the Cretaceous. Electronic Supplementary Material is available.
A large Cretaceous theropod from Patagonia, Argentina, and the evolution of carcharodontosaurids
NASA Astrophysics Data System (ADS)
Novas, Fernando E.; Valais, Silvina; Vickers-Rich, Pat; Rich, Tom
2005-05-01
The Cretaceous Carcharodontosauridae is the latest clade of carnosaurs, including the largest predatory dinosaurs yet recorded. Albeit spectacular for their size, the skeletal anatomy of these theropods remains poorly-known, and their diversity was until recently restricted to two Cenomanian species: the highly derived Giganotosaurus carolinii, from southern South America, and the incompletely known Carcharodontosaurus saharicus, from northern Africa. Here we describe an older and basal member of the group, Tyrannotitan chubutensis gen. et sp. nov., from Aptian strata of Patagonia, Argentina. The new taxon gives new insights into the systematics and evolution of carcharodontosaurids and offers a better understanding of the evolution of Southern theropod faunas. We suggest that carcharodontosaurids radiated in Gondwana sharing with spinosaurids the role of top-predators until their extinction in Cenomanian Turonian times. During this interval, the diplodocoid sauropods and giant titanosaurians went extinct (probably as part of a global-scale crisis), and the smaller abelisaurid theropods took dominance, reigning until the end of the Cretaceous. Electronic Supplementary Material is available.
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.
[Resources of Lycium species and related research progress].
Dong, Jing-Zhou; Yang, Jun-Jun; Wang, Ying
2008-09-01
Solanaceae Lycium speices are deciduous shrubs. In ancient Chinese medicine works, Lycium plants are described to work well in nourshing liver and kidney, enhancing eyesight, enriching blood, invigorating sex, reducing rheumatism and so on. More of their functions such as immunity improvement, anti-oxydation, anti-aging, anti-cancer, growth stumulation, hemopoiesis enhancing, incretion regulating, blood sugar reducing, bearing improvement and many other new functions are conformed in modern clinic researches. Lycium is also widely used in brewing, beverage and many other products. The world Lycium-related researches are mostly on Lycium species genesis and evolution, sexual evolution, active ingredient separation and pharmacological effects. The future research direction is indicated in this article, molecular evolution and systematics rather than traditional taxonomy will do better in explanation of present global distribution of Lycium species; comparative genomics research on Lycium will be a whole new way to deep gene resources exploration; relationship of genetic diversity and active ingredient variation on L. barbarum and L. chinense will lay theory basis for new germplasm development, breeding, cultivation and production regionalization.
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.
Evolution of Enzyme Superfamilies: Comprehensive Exploration of Sequence-Function Relationships.
Baier, F; Copp, J N; Tokuriki, N
2016-11-22
The sequence and functional diversity of enzyme superfamilies have expanded through billions of years of evolution from a common ancestor. Understanding how protein sequence and functional "space" have expanded, at both the evolutionary and molecular level, is central to biochemistry, molecular biology, and evolutionary biology. Integrative approaches that examine protein sequence, structure, and function have begun to provide comprehensive views of the functional diversity and evolutionary relationships within enzyme superfamilies. In this review, we outline the recent advances in our understanding of enzyme evolution and superfamily functional diversity. We describe the tools that have been used to comprehensively analyze sequence relationships and to characterize sequence and function relationships. We also highlight recent large-scale experimental approaches that systematically determine the activity profiles across enzyme superfamilies. We identify several intriguing insights from this recent body of work. First, promiscuous activities are prevalent among extant enzymes. Second, many divergent proteins retain "function connectivity" via enzyme promiscuity, which can be used to probe the evolutionary potential and history of enzyme superfamilies. Finally, we discuss open questions regarding the intricacies of enzyme divergence, as well as potential research directions that will deepen our understanding of enzyme superfamily evolution.
"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
From Ends to Causes (and Back Again) by Metaphor: The Paradox of Natural Selection
NASA Astrophysics Data System (ADS)
Blancke, Stefaan; Schellens, Tammy; Soetaert, Ronald; Van Keer, Hilde; Braeckman, Johan
2014-04-01
Natural selection is one of the most famous metaphors in the history of science. Charles Darwin used the metaphor and the underlying analogy to frame his ideas about evolution and its main driving mechanism into a full-fledged theory. Because the metaphor turned out to be such a powerful epistemic tool, Darwin naturally assumed that he could also employ it as an educational tool to inform his contemporaries about his findings. Moreover, by using the metaphor Darwin was able to bring his theory in accordance with both the dominant philosophy of science in his time and the respected tradition of natural theology. However, as he introduced his theory of evolution by natural selection in On the origin of species in 1859, the metaphor also turned out to have a serious downside. Because of its intentional overtones, his contemporaries systematically misunderstood his metaphor not as a natural mechanism causing evolution to occur but as an agent who works towards particular ends. The difference in success between natural selection as an epistemic tool and its failure as an educational tool is labelled as a paradox. We explain the paradox from a cognitive perspective and discuss the implications for teaching evolution.
The Evolution of Second-Phase Particles in 6111 Aluminum Alloy Processed by Hot and Cold Rolling
NASA Astrophysics Data System (ADS)
Zhang, Lixin; Wang, Yihan; Ni, Song; Chen, Gang; Li, Kai; Du, Yong; Song, Min
2018-03-01
The evolution of coarse Al9.9Fe2.65Ni1.45 phase, spherical Al12(Mn,Fe)3Si phase and rod-like Q phase in a 6111 aluminum alloy during hot and cold rolling deformation processes was systematically investigated in this work. The results showed that the coarse Al9.9Fe2.65Ni1.45 particles are mainly distributed at the grain boundaries, accompanied by the co-formation of Al12(Fe,Mn)3Si phase and Mg2Si phase, while the spherical Al12(Mn,Fe)3Si particles are mainly distributed in the grain interiors. Hot rolling has little effects on the size and distribution of both phases, but cold deformation can severely decrease the size of the particles by breaking the particles into small pieces. In addition, the temperature of 450 °C is not high enough for the dissolution of Q phase in the Al matrix, but the Q particles can be broken into small pieces due to the stress concentration during both hot and cold rolling deformation. In addition, the influences of phase evolution, dislocations and recrystallization on the mechanical properties evolution were also discussed.
Viscous Flow in Heavy-Ion Collisions from RHIC to LHC
NASA Astrophysics Data System (ADS)
Shen, Chun; Heinz, Ulrich
2013-05-01
We present a systematic hydrodynamic study of the evolution of hadron spectra and their azimuthal anisotropy from the lowest collision energy studied at the Relativistic Heavy Ion Collider (RHIC), s=7.7A GeV, to the highest energy reachable at the Large Hadron Collider (LHC), s=5500A GeV [C. Shen and U. Heinz, Phys. Rev. C 85, 054902 (2012) [arXiv:1202.6620 [nucl-th
Functionally conserved enhancers with divergent sequences in distant vertebrates
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yang, Song; Oksenberg, Nir; Takayama, Sachiko
To examine the contributions of sequence and function conservation in the evolution of enhancers, we systematically identified enhancers whose sequences are not conserved among distant groups of vertebrate species, but have homologous function and are likely to be derived from a common ancestral sequence. In conclusion, our approach combined comparative genomics and epigenomics to identify potential enhancer sequences in the genomes of three groups of distantly related vertebrate species.
Functionally conserved enhancers with divergent sequences in distant vertebrates
Yang, Song; Oksenberg, Nir; Takayama, Sachiko; ...
2015-10-30
To examine the contributions of sequence and function conservation in the evolution of enhancers, we systematically identified enhancers whose sequences are not conserved among distant groups of vertebrate species, but have homologous function and are likely to be derived from a common ancestral sequence. In conclusion, our approach combined comparative genomics and epigenomics to identify potential enhancer sequences in the genomes of three groups of distantly related vertebrate species.
Photosynthetic production of hydrogen. [Blue-green alga, Anabaena cylindrica
DOE Office of Scientific and Technical Information (OSTI.GOV)
Neil, G.; Nicholas, D.J.D.; Bockris, J.O.
A systematic investigation of photosynthetic hydrogen production using a blue-green alga, Anabaena cylindrica, was carried out. The results indicate that there are two important problems which must be overcome for large-scale hydrogen production using photosynthetic processes. These are (a) the development of a stable system, and (b) attainment of at least a fifty-fold increase in the rate of hydrogen evolution per unit area illuminated.
Cryptic bioactivity capacitated by synthetic hybrid plant peptides
Hirakawa, Yuki; Shinohara, Hidefumi; Welke, Kai; Irle, Stephan; Matsubayashi, Yoshikatsu; Torii, Keiko U.; Uchida, Naoyuki
2017-01-01
Evolution often diversifies a peptide hormone family into multiple subfamilies, which exert distinct activities by exclusive interaction with specific receptors. Here we show that systematic swapping of pre-existing variation in a subfamily of plant CLE peptide hormones leads to a synthetic bifunctional peptide that exerts activities beyond the original subfamily by interacting with multiple receptors. This approach provides new insights into the complexity and specificity of peptide signalling. PMID:28165456
Life Cycle Evolution and Systematics of Campanulariid Hydrozoans
2004-09-01
kit according to manufacturer’s protocol. Purified PCR product was cycle-sequenced using either Big Dye 2 or 3 sequencing chemistry (ABI), following...ethidium bromide and purified with PCR purification kits (Qiagen). Purified products were cycle- sequenced with either Big Dye 2 or 3 sequencing chemistry...PCR purification kit (Qiagen). The purified product was cycle-sequenced using Big Dye 2 sequencing chemistry (ABI) following the manufacturer’s
NASA Astrophysics Data System (ADS)
Tonegawa, Motonari; Okumura, Teppei; Totani, Tomonori; Dalton, Gavin; Glazebrook, Karl; Yabe, Kiyoto
2018-06-01
Intrinsic alignments (IA), the coherent alignment of intrinsic galaxy orientations, can be a source of a systematic error of weak lensing surveys. The redshift evolution of IA also contains information about the physics of galaxy formation and evolution. This paper presents the first measurement of IA at high redshift, z ˜ 1.4, using the spectroscopic catalog of blue star-forming galaxies of the FastSound redshift survey, with the galaxy shape information from the Canada-Hawaii-France telescope lensing survey. The IA signal is consistent with zero with power-law amplitudes fitted to the projected correlation functions for density-shape and shape-shape correlation components, Aδ+ = -0.0071 ± 0.1340 and A++ = -0.0505 ± 0.0848, respectively. These results are consistent with those obtained from blue galaxies at lower redshifts (e.g., A _{δ +}=0.0035_{-0.0389}^{+0.0387} and A_{++}=0.0045_{-0.0168}^{+0.0166} at z = 0.51 from the WiggleZ survey). The upper limit of the constrained IA amplitude corresponds to a few percent contamination to the weak-lensing shear power spectrum, resulting in systematic uncertainties on the cosmological parameter estimations by -0.052 < Δσ8 < 0.039 and -0.039 < ΔΩm < 0.030.
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.
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.
Galaxy-galaxy lensing in the Dark Energy Survey Science Verification data
NASA Astrophysics Data System (ADS)
Clampitt, J.; Sánchez, C.; Kwan, J.; Krause, E.; MacCrann, N.; Park, Y.; Troxel, M. A.; Jain, B.; Rozo, E.; Rykoff, E. S.; Wechsler, R. H.; Blazek, J.; Bonnett, C.; Crocce, M.; Fang, Y.; Gaztanaga, E.; Gruen, D.; Jarvis, M.; Miquel, R.; Prat, J.; Ross, A. J.; Sheldon, E.; Zuntz, J.; Abbott, T. M. C.; Abdalla, F. B.; Armstrong, R.; Becker, M. R.; Benoit-Lévy, A.; Bernstein, G. M.; Bertin, E.; Brooks, D.; Burke, D. L.; Carnero Rosell, A.; Carrasco Kind, M.; Cunha, C. E.; D'Andrea, C. B.; da Costa, L. N.; Desai, S.; Diehl, H. T.; Dietrich, J. P.; Doel, P.; Estrada, J.; Evrard, A. E.; Fausti Neto, A.; Flaugher, B.; Fosalba, P.; Frieman, J.; Gruendl, R. A.; Honscheid, K.; James, D. J.; Kuehn, K.; Kuropatkin, N.; Lahav, O.; Lima, M.; March, M.; Marshall, J. L.; Martini, P.; Melchior, P.; Mohr, J. J.; Nichol, R. C.; Nord, B.; Plazas, A. A.; Romer, A. K.; Sanchez, E.; Scarpine, V.; Schubnell, M.; Sevilla-Noarbe, I.; Smith, R. C.; Soares-Santos, M.; Sobreira, F.; Suchyta, E.; Swanson, M. E. C.; Tarle, G.; Thomas, D.; Vikram, V.; Walker, A. R.
2017-03-01
We present galaxy-galaxy lensing results from 139 deg2 of Dark Energy Survey (DES) Science Verification (SV) data. Our lens sample consists of red galaxies, known as redMaGiC, which are specifically selected to have a low photometric redshift error and outlier rate. The lensing measurement has a total signal-to-noise ratio of 29 over scales 0.09 < R < 15 Mpc h-1, including all lenses over a wide redshift range 0.2 < z < 0.8. Dividing the lenses into three redshift bins for this constant moving number density sample, we find no evidence for evolution in the halo mass with redshift. We obtain consistent results for the lensing measurement with two independent shear pipelines, NGMIX and IM3SHAPE. We perform a number of null tests on the shear and photometric redshift catalogues and quantify resulting systematic uncertainties. Covariances from jackknife subsamples of the data are validated with a suite of 50 mock surveys. The result and systematic checks in this work provide a critical input for future cosmological and galaxy evolution studies with the DES data and redMaGiC galaxy samples. We fit a halo occupation distribution (HOD) model, and demonstrate that our data constrain the mean halo mass of the lens galaxies, despite strong degeneracies between individual HOD parameters.
SOLAR WIND HEAVY IONS OVER SOLAR CYCLE 23: ACE/SWICS MEASUREMENTS
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lepri, S. T.; Landi, E.; Zurbuchen, T. H.
2013-05-01
Solar wind plasma and compositional properties reflect the physical properties of the corona and its evolution over time. Studies comparing the previous solar minimum with the most recent, unusual solar minimum indicate that significant environmental changes are occurring globally on the Sun. For example, the magnetic field decreased 30% between the last two solar minima, and the ionic charge states of O have been reported to change toward lower values in the fast wind. In this work, we systematically and comprehensively analyze the compositional changes of the solar wind during cycle 23 from 2000 to 2010 while the Sun movedmore » from solar maximum to solar minimum. We find a systematic change of C, O, Si, and Fe ionic charge states toward lower ionization distributions. We also discuss long-term changes in elemental abundances and show that there is a {approx}50% decrease of heavy ion abundances (He, C, O, Si, and Fe) relative to H as the Sun went from solar maximum to solar minimum. During this time, the relative abundances in the slow wind remain organized by their first ionization potential. We discuss these results and their implications for models of the evolution of the solar atmosphere, and for the identification of the fast and slow wind themselves.« less
NASA Astrophysics Data System (ADS)
Tonegawa, Motonari; Okumura, Teppei; Totani, Tomonori; Dalton, Gavin; Glazebrook, Karl; Yabe, Kiyoto
2018-04-01
Intrinsic alignments (IA), the coherent alignment of intrinsic galaxy orientations, can be a source of a systematic error of weak lensing surveys. The redshift evolution of IA also contains information about the physics of galaxy formation and evolution. This paper presents the first measurement of IA at high redshift, z ˜ 1.4, using the spectroscopic catalog of blue star-forming galaxies of the FastSound redshift survey, with the galaxy shape information from the Canada-Hawaii-France telescope lensing survey. The IA signal is consistent with zero with power-law amplitudes fitted to the projected correlation functions for density-shape and shape-shape correlation components, Aδ+ = -0.0071 ± 0.1340 and A++ = -0.0505 ± 0.0848, respectively. These results are consistent with those obtained from blue galaxies at lower redshifts (e.g., A _{δ +}=0.0035_{-0.0389}^{+0.0387} and A_{++}=0.0045_{-0.0168}^{+0.0166} at z = 0.51 from the WiggleZ survey). The upper limit of the constrained IA amplitude corresponds to a few percent contamination to the weak-lensing shear power spectrum, resulting in systematic uncertainties on the cosmological parameter estimations by -0.052 < Δσ8 < 0.039 and -0.039 < ΔΩm < 0.030.
Systems Science and Childhood Obesity: A Systematic Review and New Directions
Foster, E. Michael
2013-01-01
As a public health problem, childhood obesity operates at multiple levels, ranging from individual health behaviors to school and community characteristics to public policies. Examining obesity, particularly childhood obesity, from any single perspective is likely to fail, and systems science methods offer a possible solution. We systematically reviewed studies that examined the causes and/or consequences of obesity from a systems science perspective. The 21 included studies addressed four general areas of systems science in obesity: (1) translating interventions to a large scale, (2) the effect of obesity on other health or economic outcomes, (3) the effect of geography on obesity, and (4) the effect of social networks on obesity. In general, little research addresses obesity from a true, integrated systems science perspective, and the available research infrequently focuses on children. This shortcoming limits the ability of that research to inform public policy. However, we believe that the largely incremental approaches used in current systems science lay a foundation for future work and present a model demonstrating the system of childhood obesity. Systems science perspective and related methods are particularly promising in understanding the link between childhood obesity and adult outcomes. Systems models emphasize the evolution of agents and their interactions; such evolution is particularly salient in the context of a developing child. PMID:23710344
NASA Technical Reports Server (NTRS)
Nakamura, N.; Unruh, D. M.; Tatsumoto, M.; Hutchison, R.
1982-01-01
Analyses of whole rock and mineral separates from the Nakhla meteorite are carried out by means of Sm-Nd and U-Tn-Pb systematics and by determining their REE, Ba, Sr, Rb, and K concentrations. Results show that the Sm-Nd age of the meteorite is 1.26 + or - 0.7 b.y., while the high initial epsilon(Nd) value of +16 suggests that Nakhla was derived from a light REE-depleted, old planetary mantle source. A three-stage Sm-Nd evolution model is developed and used in combination with LIL element data and estimated partition coefficients in order to test partial melting and fractional crystallization models and to estimate LIL abundances in a possible Nakhla source. The calculations indicate that partial melting of the source followed by extensive fractional crystallization of the partial melt could account for the REE abundances in the Nakhla constituent minerals. It is concluded that the significantly younger age of Nakhla than the youngest lunar rock, the young differentiation age inferred from U-Th-Pb data, and the estimated LIL abundances suggest that this meteorite may have been derived from a relatively large, well-differentiated planetary body such as Mars.
Quasars, clusters and cosmology
NASA Astrophysics Data System (ADS)
Dhanda, Neelam
PART A: Acceleration of the Universe and Modified Gravity: We study the power of next-generation galaxy cluster surveys (such as eROSITA and WFXT) in constraining the cosmological parameters and especially the growth history of the Universe, using the information from galaxy cluster redshift and mass-function evolution and from cluster power spectrum. We use the Fisher Matrix formalism to evaluate the potential for the galaxy cluster surveys to make predictions about cosmological parameters like the gravitational growth index gamma. The primary purpose of this study has been to check whether we can rule out one or the other of the underlying gravity theories in light of the present uncertainty of mass-observable relations and their scatter evolution. We found that these surveys will provide better constraints on various cosmological parameters even after we admit a lack of complete knowledge about the galaxy cluster structure, and when we combine the information from the cluster number count redshift and mass evolution with that from the cluster power spectrum. Based on this, we studied the ability of different surveys to constrain the growth history of the Universe. It was found that whereas eROSITA surveys will need strong priors on cluster structure evolution to conclusively rule out one or the other of the two gravity models, General Relativity and DGP Braneworld Gravity; WFXT surveys do hold the special promise of differentiating growth and telling us whether it is GR or not, with its wide-field survey having the ability to say so even with 99% confidence. PART B: Chemical Evolution in Quasars: We studied chemical evolution in the broad emission line region (BELR) of nitrogen rich quasars drawn from the SDSS Quasar Catalogue IV. Using tools of emission-line spectroscopy, we made detailed abundance measurements of ˜ 40 quasars and estimated their metallicities using the line-intensity ratio method. It was found that quasars with strong nitrogen lines are indicators of high metallicities. Some of these quasars have reached metallicities as high as Z ˜ 20 Z⊙ . Our detailed analysis showed that except in three QSOs, most of the different line-intensity ratios implied the similar metallicities. This verifies that this abundance analysis technique does produce meaningful results. The exceptions are the line-intensity ratio NIV]/CIV, which gives systematically low metallicities and the line-intensity ratio NV/He II, which gives systematically high metallicities. We compared our findings with the predictions of the galactic chemical evolution models. From this study it was concluded that such high metallicities are reached either by requiring a top-heavy Initial Mass Function (IMF) for the quasar host galaxy as suggested by theoretical models, or by physically catastrophic events such as mergers that trigger star formation in already evolved systems which then leads to extreme metallicities in such quasars.
Wranik, W Dominika; Gambold, Liesl; Hanson, Natasha; Levy, Adrian
2017-04-01
Public reimbursement of drugs is a costly proposition for health care systems. Decisions to add drugs to the public formulary are often guided by review processes and committees. The evolution of the formulary review process in Canada's publicly funded health system is characterized by increased centralization and systematization. In the past, the review of evidence and recommendation was conducted at the regional level, but was replaced with the pan-Canadian Oncology Drug Review in 2011. We assess the extent to which centralization and systematization of the review process have responded to past challenges, focusing on the use of economic evaluation in the process. Past challenges with economic evaluation experienced by regionalized review committees were identified from literature and qualitative data collected in the province of Nova Scotia. We categorize these using a typology with a macro-, meso, and micro-level hierarchy, which provides a useful framework for understanding at which level change is required, and who has the authority to influence change. Using grounded theory methods, we identify approaches used by Nova Scotia past committee members to compensate for perceived shortcomings of the process. These include an undue reliance on other committee members, on the multidisciplinarity of the committee, and on past decisions. Using a policy analysis approach, we argue that centralization and systematization of the review process only partially address the shortcomings of the previous regionalized process. Lessons from Canada can inform policy discussions across all health systems, where similar challenges with the formulary review process have been identified. © 2016 The Authors. The International Journal of Health Planning and Management published by John Wiley & Sons Ltd. © 2016 The Authors. The International Journal of Health Planning and Management published by John Wiley & Sons Ltd.
Systematic analysis and evolution of 5S ribosomal DNA in metazoans.
Vierna, J; Wehner, S; Höner zu Siederdissen, C; Martínez-Lage, A; Marz, M
2013-11-01
Several studies on 5S ribosomal DNA (5S rDNA) have been focused on a subset of the following features in mostly one organism: number of copies, pseudogenes, secondary structure, promoter and terminator characteristics, genomic arrangements, types of non-transcribed spacers and evolution. In this work, we systematically analyzed 5S rDNA sequence diversity in available metazoan genomes, and showed organism-specific and evolutionary-conserved features. Putatively functional sequences (12,766) from 97 organisms allowed us to identify general features of this multigene family in animals. Interestingly, we show that each mammal species has a highly conserved (housekeeping) 5S rRNA type and many variable ones. The genomic organization of 5S rDNA is still under debate. Here, we report the occurrence of several paralog 5S rRNA sequences in 58 of the examined species, and a flexible genome organization of 5S rDNA in animals. We found heterogeneous 5S rDNA clusters in several species, supporting the hypothesis of an exchange of 5S rDNA from one locus to another. A rather high degree of variation of upstream, internal and downstream putative regulatory regions appears to characterize metazoan 5S rDNA. We systematically studied the internal promoters and described three different types of termination signals, as well as variable distances between the coding region and the typical termination signal. Finally, we present a statistical method for detection of linkage among noncoding RNA (ncRNA) gene families. This method showed no evolutionary-conserved linkage among 5S rDNAs and any other ncRNA genes within Metazoa, even though we found 5S rDNA to be linked to various ncRNAs in several clades.
Systematic analysis and evolution of 5S ribosomal DNA in metazoans
Vierna, J; Wehner, S; Höner zu Siederdissen, C; Martínez-Lage, A; Marz, M
2013-01-01
Several studies on 5S ribosomal DNA (5S rDNA) have been focused on a subset of the following features in mostly one organism: number of copies, pseudogenes, secondary structure, promoter and terminator characteristics, genomic arrangements, types of non-transcribed spacers and evolution. In this work, we systematically analyzed 5S rDNA sequence diversity in available metazoan genomes, and showed organism-specific and evolutionary-conserved features. Putatively functional sequences (12 766) from 97 organisms allowed us to identify general features of this multigene family in animals. Interestingly, we show that each mammal species has a highly conserved (housekeeping) 5S rRNA type and many variable ones. The genomic organization of 5S rDNA is still under debate. Here, we report the occurrence of several paralog 5S rRNA sequences in 58 of the examined species, and a flexible genome organization of 5S rDNA in animals. We found heterogeneous 5S rDNA clusters in several species, supporting the hypothesis of an exchange of 5S rDNA from one locus to another. A rather high degree of variation of upstream, internal and downstream putative regulatory regions appears to characterize metazoan 5S rDNA. We systematically studied the internal promoters and described three different types of termination signals, as well as variable distances between the coding region and the typical termination signal. Finally, we present a statistical method for detection of linkage among noncoding RNA (ncRNA) gene families. This method showed no evolutionary-conserved linkage among 5S rDNAs and any other ncRNA genes within Metazoa, even though we found 5S rDNA to be linked to various ncRNAs in several clades. PMID:23838690
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
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.
Quantification provides a conceptual basis for convergent evolution.
Speed, Michael P; Arbuckle, Kevin
2017-05-01
While much of evolutionary biology attempts to explain the processes of diversification, there is an important place for the study of phenotypic similarity across life forms. When similar phenotypes evolve independently in different lineages this is referred to as convergent evolution. Although long recognised, evolutionary convergence is receiving a resurgence of interest. This is in part because new genomic data sets allow detailed and tractable analysis of the genetic underpinnings of convergent phenotypes, and in part because of renewed recognition that convergence may reflect limitations in the diversification of life. In this review we propose that although convergent evolution itself does not require a new evolutionary framework, none the less there is room to generate a more systematic approach which will enable evaluation of the importance of convergent phenotypes in limiting the diversity of life's forms. We therefore propose that quantification of the frequency and strength of convergence, rather than simply identifying cases of convergence, should be considered central to its systematic comprehension. We provide a non-technical review of existing methods that could be used to measure evolutionary convergence, bringing together a wide range of methods. We then argue that quantification also requires clear specification of the level at which the phenotype is being considered, and argue that the most constrained examples of convergence show similarity both in function and in several layers of underlying form. Finally, we argue that the most important and impressive examples of convergence are those that pertain, in form and function, across a wide diversity of selective contexts as these persist in the likely presence of different selection pressures within the environment. © 2016 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.
Davatzes, N.C.; Eichhubl, P.; Aydin, A.
2005-01-01
Faults in sandstone are frequently composed of two classes of structures: (1) deformation bands and (2) joints and sheared joints. Whereas the former structures are associated with cataclastic deformation, the latter ones represent brittle fracturing, fragmentation, and brecciation. We investigated the distribution of these structures, their formation, and the underlying mechanical controls for their occurrence along the Moab normal fault in southeastern Utah through the use of structural mapping and numerical elastic boundary element modeling. We found that deformation bands occur everywhere along the fault, but with increased density in contractional relays. Joints and sheared joints only occur at intersections and extensional relays. In all locations , joints consistently overprint deformation bands. Localization of joints and sheared joints in extensional relays suggests that their distribution is controlled by local variations in stress state that are due to mechanical interaction between the fault segments. This interpretation is consistent with elastic boundary element models that predict a local reduction in mean stress and least compressive principal stress at intersections and extensional relays. The transition from deformation band to joint formation along these sections of the fault system likely resulted from the combined effects of changes in remote tectonic loading, burial depth, fluid pressure, and rock properties. In the case of the Moab fault, we conclude that the structural heterogeneity in the fault zone is systematically related to the geometric evolution of the fault, the local state of stress associated with fault slip , and the remote loading history. Because the type and distribution of structures affect fault permeability and strength, our results predict systematic variations in these parameters with fault evolution. ?? 2004 Geological Society of America.
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.
NASA Astrophysics Data System (ADS)
Kumari, Seema; Paul, Debajyoti; Stracke, Andreas
2016-12-01
An open system evolutionary model of the Earth, comprising continental crust (CC), upper and lower mantle (UM, LM), and an additional isolated reservoir (IR) has been developed to study the isotopic evolution of the silicate Earth. The model is solved numerically at 1 Myr time steps over 4.55 Gyr of Earth history to reproduce both the present-day concentrations and isotope ratios of key radioactive decay systems (Rb-Sr, Sm-Nd, and U-Th-Pb) in these terrestrial reservoirs. Various crustal growth scenarios - continuous versus episodic and early versus late crustal growth - and their effect on the evolution of Sr-Nd-Pb isotope systematics in the silicate reservoirs have been evaluated. Modeling results where the present-day UM is ∼60% of the total mantle mass and a lower mantle that is non-primitive reproduce the estimated geochemical composition and isotope ratios in Earth's silicate reservoirs. The isotopic evolution of the silicate Earth is strongly affected by the mode of crustal growth; only an exponential crustal growth pattern with crustal growth since the early Archean satisfactorily explains the chemical and isotopic evolution of the crust-mantle system and accounts for the so-called Pb paradoxes. Assuming that the OIB source is located in the deeper mantle, our model could, however, not reproduce its target ɛNd of +4.6 for the UM, which has been estimated from the average isotope ratios of 32 individual ocean island localities. Hence, either mantle plumes sample the LM in a non-representative way, or the simplified model set-up does not capture the full complexity of Earth's lower mantle (Nd isotope) evolution. Compared to the results obtained for a 4.55 Ga Earth, a model assuming a protracted U-Pb evolution of silicate Earth by ca. 100 Myr reproduces a slightly better fit for the Pb isotope ratios in Earth's silicate reservoirs. One notable feature of successful models is the early depletion of incompatible elements (as well as rapid decrease in Th/U) in the UM within the initial 500 Myr, as a result of early formation of CC, which supports other evidence in favor of the presence of Hadean continental crust. Therefore, a chondritic Th/U ratio (4 ± 0.2) in the UM until 2 Gyr appears rather unlikely. We find that the κ conundrum - the observation that measured Th/U ratios and those deduced from 208Pb-206Pb isotope systematics differ - is a natural outcome of an open system evolution in which preferential recycling of U for the past 2 Gyr has played a dominant role. Overall, our simulations strongly favor exponential crustal growth, starting in the early Hadean, the transient preservation of compositionally distinct mantle reservoirs over billion year time periods, and a generally less incompatible element depleted, but non-primitive composition of the lower mantle.
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.
Participation costs can suppress the evolution of upstream reciprocity.
Peña, Jorge; Pestelacci, Enea; Berchtold, André; Tomassini, Marco
2011-03-21
Indirect reciprocity, one of the many mechanisms proposed to explain the evolution of cooperation, is the idea that altruistic actions can be rewarded by third parties. Upstream or generalized reciprocity is one type of indirect reciprocity in which individuals help someone if they have been helped by somebody else in the past. Although empirically found to be at work in humans, the evolution of upstream reciprocity is difficult to explain from a theoretical point of view. A recent model of upstream reciprocity, first proposed by Nowak and Roch (2007) and further analyzed by Iwagami and Masuda (2010), shows that while upstream reciprocity alone does not lead to the evolution of cooperation, it can act in tandem with mechanisms such as network reciprocity and increase the total level of cooperativity in the population. We argue, however, that Nowak and Roch's model systematically leads to non-uniform interaction rates, where more cooperative individuals take part in more games than less cooperative ones. As a result, the critical benefit-to-cost ratios derived under this model in previous studies are not invariant with respect to the addition of participation costs. We show that accounting for these costs can hinder and even suppress the evolution of upstream reciprocity, both for populations with non-random encounters and graph-structured populations. Copyright © 2011 Elsevier Ltd. All rights reserved.
Post-rift magmatic evolution of the eastern North American “passive-aggressive” margin
Mazza, Sarah E.; Gazel, Esteban; Johnson, Elizabeth A.; Bizmis, Michael; McAleer, Ryan J.; Biryol, C. Berk
2017-01-01
Understanding the evolution of passive margins requires knowledge of temporal and chemical constraints on magmatism following the transition from supercontinent to rifting, to post-rifting evolution. The Eastern North American Margin (ENAM) is an ideal study location as several magmatic pulses occurred in the 200 My following rifting. In particular, the Virginia-West Virginia region of the ENAM has experienced two postrift magmatic pulses at ∼152 Ma and 47 Ma, and thus provides a unique opportunity to study the long-term magmatic evolution of passive margins. Here we present a comprehensive set of geochemical data that includes new 40Ar/39Ar ages, major and trace-element compositions, and analysis of radiogenic isotopes to further constrain their magmatic history. The Late Jurassic volcanics are bimodal, from basanites to phonolites, while the Eocene volcanics range from picrobasalt to rhyolite. Modeling suggests that the felsic volcanics from both the Late Jurassic and Eocene events are consistent with fractional crystallization. Sr-Nd-Pb systematics for the Late Jurassic event suggests HIMU and EMII components in the magma source that we interpret as upper mantle components rather than crustal interaction. Lithospheric delamination is the best hypothesis for magmatism in Virginia/West Virginia, due to tectonic instabilities that are remnant from the long-term evolution of this margin, resulting in a “passive-aggressive” margin that records multiple magmatic events long after rifting ended.
Rothwell, Gar W; Wyatt, Sarah E; Tomescu, Alexandru M F
2014-06-01
Paleontology yields essential evidence for inferring not only the pattern of evolution, but also the genetic basis of evolution within an ontogenetic framework. Plant fossils provide evidence for the pattern of plant evolution in the form of transformational series of structure through time. Developmentally diagnostic structural features that serve as "fingerprints" of regulatory genetic pathways also are preserved by plant fossils, and here we provide examples of how those fingerprints can be used to infer the mechanisms by which plant form and development have evolved. When coupled with an understanding of variations and systematic distributions of specific regulatory genetic pathways, this approach provides an avenue for testing evolutionary hypotheses at the organismal level that is analogous to employing bioinformatics to explore genetics at the genomic level. The positions where specific genes, gene families, and developmental regulatory mechanisms first appear in phylogenies are correlated with the positions where fossils with the corresponding structures occur on the tree, thereby yielding testable hypotheses that extend our understanding of the role of developmental changes in the evolution of the body plans of vascular plant sporophytes. As a result, we now have new and powerful methodologies for characterizing major evolutionary changes in morphology, anatomy, and physiology that have resulted from combinations of genetic regulatory changes and that have produced the synapomorphies by which we recognize major clades of plants. © 2014 Botanical Society of America, Inc.
Linkage of A-to-I RNA Editing in Metazoans and the Impact on Genome Evolution.
Duan, Yuange; Dou, Shengqian; Zhang, Hong; Wu, Changcheng; Wu, Mingming; Lu, Jian
2018-01-01
The adenosine-to-inosine (A-to-I) RNA editomes have been systematically characterized in various metazoan species, and many editing sites were found in clusters. However, it remains unclear whether the clustered editing sites tend to be linked in the same RNA molecules or not. By adopting a method originally designed to detect linkage disequilibrium of DNA mutations, we examined the editomes of ten metazoan species and detected extensive linkage of editing in Drosophila and cephalopods. The prevalent linkages of editing in these two clades, many of which are conserved between closely related species and might be associated with the adaptive proteomic recoding, are maintained by natural selection at the cost of genome evolution. Nevertheless, in worms and humans, we only detected modest proportions of linked editing events, the majority of which were not conserved. Furthermore, the linkage of editing in coding regions of worms and humans might be overall deleterious, which drives the evolution of DNA sites to escape promiscuous editing. Altogether, our results suggest that the linkage landscape of A-to-I editing has evolved during metazoan evolution. This present study also suggests that linkage of editing should be considered in elucidating the functional consequences of RNA editing. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
Combining use of a panel of ssDNA aptamers in the detection of Staphylococcus aureus
Cao, Xiaoxiao; Li, Shaohua; Chen, Liucun; Ding, Hongmei; Xu, Hua; Huang, Yanping; Li, Jie; Liu, Nongle; Cao, Weihong; Zhu, Yanjun; Shen, Beifen; Shao, Ningsheng
2009-01-01
In this article, a panel of ssDNA aptamers specific to Staphylococcus aureus was obtained by a whole bacterium-based SELEX procedure and applied to probing S. aureus. After several rounds of selection with S. aureus as the target and Streptococcus and S. epidermidis as counter targets, the highly enriched oligonucleic acid pool was sequenced and then grouped under different families on the basis of the homology of the primary sequence and the similarity of the secondary structure. Eleven sequences from different families were selected for further characterization by confocal imaging and flow cytometry analysis. Results showed that five aptamers demonstrated high specificity and affinity to S. aureus individually. The five aptamers recognize different molecular targets by competitive experiment. Combining these five aptamers had a much better effect than the individual aptamer in the recognition of different S. aureus strains. In addition, the combined aptamers can probe single S. aureus in pyogenic fluids. Our work demonstrates that a set of aptamers specific to one bacterium can be used in combination for the identification of the bacterium instead of a single aptamer. PMID:19498077
Combining use of a panel of ssDNA aptamers in the detection of Staphylococcus aureus.
Cao, Xiaoxiao; Li, Shaohua; Chen, Liucun; Ding, Hongmei; Xu, Hua; Huang, Yanping; Li, Jie; Liu, Nongle; Cao, Weihong; Zhu, Yanjun; Shen, Beifen; Shao, Ningsheng
2009-08-01
In this article, a panel of ssDNA aptamers specific to Staphylococcus aureus was obtained by a whole bacterium-based SELEX procedure and applied to probing S. aureus. After several rounds of selection with S. aureus as the target and Streptococcus and S. epidermidis as counter targets, the highly enriched oligonucleic acid pool was sequenced and then grouped under different families on the basis of the homology of the primary sequence and the similarity of the secondary structure. Eleven sequences from different families were selected for further characterization by confocal imaging and flow cytometry analysis. Results showed that five aptamers demonstrated high specificity and affinity to S. aureus individually. The five aptamers recognize different molecular targets by competitive experiment. Combining these five aptamers had a much better effect than the individual aptamer in the recognition of different S. aureus strains. In addition, the combined aptamers can probe single S. aureus in pyogenic fluids. Our work demonstrates that a set of aptamers specific to one bacterium can be used in combination for the identification of the bacterium instead of a single aptamer.
Aptamer-based impedimetric sensor for bacterial typing.
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
2012-10-02
The development of an aptamer-based impedimetric sensor for typing of bacteria (AIST-B) is presented. Highly specific DNA aptamers to Salmonella enteritidis were selected via Cell-SELEX technique. Twelve rounds of selection were performed; each comprises a positive selection step against S. enteritidis and a negative selection step against a mixture of related pathogens, including Salmonella typhimurium, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Citrobacter freundii, to ensure the species-specificity of the selected aptamers. After sequencing of the pool showing the highest binding affinity to S. enteritidis, a DNA sequence of high affinity to the bacteria was integrated into an impedimetric sensor via self-assembly onto a gold nanoparticles-modified screen-printed carbon electrode (GNPs-SPCE). Remarkably, this aptasensor is highly selective and can successfully detect S. enteritidis down to 600 CFU mL(-1) (equivalent to 18 CFU in 30 μL assay volume) in 10 min and distinguish it from other Salmonella species, including S. typhimurium and S. choleraesuis. This report is envisaged to open a new venue for the aptamer-based typing of a variety of microorganisms using a rapid, economic, and label-free electrochemical platform.
The next generation in aircraft protection against advanced MANPADS
NASA Astrophysics Data System (ADS)
Chapman, Stuart
2014-10-01
This paper discusses the advanced and novel technologies and underlying systems capabilities that Selex ES has applied during the development, test and evaluation of the twin head Miysis DIRCM System in order to ensure that it provides the requisite levels of protection against the latest, sophisticated all-aspect IR MANPADS. The importance of key performance parameters, including the fundamental need for "spherical" coverage, rapid time to energy-on-target, laser tracking performance and radiant intensity on seeker dome is covered. It also addresses the approach necessary to ensure that the equipment is suited to all air platforms from the smallest helicopters to large transports, while also ensuring that it achieves an inherent high reliability and an ease of manufacture and repair such that a step change in through-life cost in comparison to previous generation systems can be achieved. The benefits and issues associated with open architecture design are also considered. Finally, the need for extensive test and evaluation at every stage, including simulation, laboratory testing, platform and target dynamic testing in a System Integration Laboratory (SIL), flight trial, missile live-fire, environmental testing and reliability testing is also described.
G-Quadruplex Forming Oligonucleotides as Anti-HIV Agents.
Musumeci, Domenica; Riccardi, Claudia; Montesarchio, Daniela
2015-09-22
Though a variety of different non-canonical nucleic acids conformations have been recognized, G-quadruplex structures are probably the structural motifs most commonly found within known oligonucleotide-based aptamers. This could be ascribed to several factors, as their large conformational diversity, marked responsiveness of their folding/unfolding processes to external stimuli, high structural compactness and chemo-enzymatic and thermodynamic stability. A number of G-quadruplex-forming oligonucleotides having relevant in vitro anti-HIV activity have been discovered in the last two decades through either SELEX or rational design approaches. Improved aptamers have been obtained by chemical modifications of natural oligonucleotides, as terminal conjugations with large hydrophobic groups, replacement of phosphodiester linkages with phosphorothioate bonds or other surrogates, insertion of base-modified monomers, etc. In turn, detailed structural studies have elucidated the peculiar architectures adopted by many G-quadruplex-based aptamers and provided insight into their mechanism of action. An overview of the state-of-the-art knowledge of the relevance of putative G-quadruplex forming sequences within the viral genome and of the most studied G-quadruplex-forming aptamers, selectively targeting HIV proteins, is here presented.
Improvement of the Power Control Unit for Ion Thruster to Cope with Milli-Newton Range RIT
NASA Astrophysics Data System (ADS)
Ceruti, Luca; Polli, Aldo; Galantini, Paolo
2014-08-01
The recent development and testing activities of a miniaturized Radio-Frequency Ion Thruster, with relevant ancillary elements, in the range of 10 to 100 micro-Newtons, joined with past flight heritage in the milli-Newton range (RIT-10 for Artemis), shows an appealing capability of such an electrical propulsion technology to support thrust in a wide range of space applications from very fine attitude control up to deorbiting of small-medium satellites. As expectable, this implies that the mentioned ancillary elements (mainly Radio-Frequency Generator and Power Control Unit) require adaptation to the different requirements imposed to different missions and thrust ranges. Regarding the Power Control Unit different power levels, both the controllability requirements and the spacecraft interfaces impose non negligible adaptation leading to significant increase of development activities and associated cost (nonrecurring) increase. From that and with the main purpose to minimize such impacts and provide reliable equipments, Selex ES since a few years is devoting maximum attention in the incremental innovation of the existing design in order to maximize their reuse.
Sicco, Estefanía; Báez, Jessica; Margenat, Jimena; García, Fernanda; Ibarra, Manuel; Cabral, Pablo; Moreno, María; Cerecetto, Hugo; Calzada, Victoria
2018-03-01
Aptamers, oligonucleotides with the capability to bind to a target through non-covalent bonds with high affinity and specificity, have a great number of advantages as scaffold to prepare molecular imaging agents. In this sense, we have performed post-SELEX modifications of a truncated aptamer, Sgc8-c, which bind to protein tyrosine kinase 7 to obtain a specific molecular targeting probe for in vivo diagnosis and in vivo therapy. Herein, we describe the synthetic efforts to prepare conjugates between Sgc8-c and different metallic ions chelator moieties in short times, high purities, and adequate yields. The selected chelator moieties, derived from 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, 2-benzyl-1,4,7-triazacyclononane-1,4,7-triacetic acid, and 6-hydrazinonicotinic acid, were covalently attached at the 5'-aptamer position yielding the expected products which were stable in aqueous solution up to 75°C and in typical aptamer storage conditions at least for 30 days. © 2017 John Wiley & Sons A/S.
Prakash, Aishwarya; Natarajan, Amarnath; Marky, Luis A.; Ouellette, Michel M.; Borgstahl, Gloria E. O.
2011-01-01
Replication protein A (RPA), a key player in DNA metabolism, has 6 single-stranded DNA-(ssDNA-) binding domains (DBDs) A-F. SELEX experiments with the DBDs-C, -D, and -E retrieve a 20-nt G-quadruplex forming sequence. Binding studies show that RPA-DE binds preferentially to the G-quadruplex DNA, a unique preference not observed with other RPA constructs. Circular dichroism experiments show that RPA-CDE-core can unfold the G-quadruplex while RPA-DE stabilizes it. Binding studies show that RPA-C binds pyrimidine- and purine-rich sequences similarly. This difference between RPA-C and RPA-DE binding was also indicated by the inability of RPA-CDE-core to unfold an oligonucleotide containing a TC-region 5′ to the G-quadruplex. Molecular modeling studies of RPA-DE and telomere-binding proteins Pot1 and Stn1 reveal structural similarities between the proteins and illuminate potential DNA-binding sites for RPA-DE and Stn1. These data indicate that DBDs of RPA have different ssDNA recognition properties. PMID:21772997
AO WFS detector developments at ESO to prepare for the E-ELT
NASA Astrophysics Data System (ADS)
Downing, Mark; Casali, Mark; Finger, Gert; Lewis, Steffan; Marchetti, Enrico; Mehrgan, Leander; Ramsay, Suzanne; Reyes, Javier
2016-07-01
ESO has a very active on-going AO WFS detector development program to not only meet the needs of the current crop of instruments for the VLT, but also has been actively involved in gathering requirements, planning, and developing detectors and controllers/cameras for the instruments in design and being proposed for the E-ELT. This paper provides an overall summary of the AO WFS Detector requirements of the E-ELT instruments currently in design and telescope focal units. This is followed by a description of the many interesting detector, controller, and camera developments underway at ESO to meet these needs; a) the rationale behind and plan to upgrade the 240x240 pixels, 2000fps, "zero noise", L3Vision CCD220 sensor based AONGC camera; b) status of the LGSD/NGSD High QE, 3e- RoN, fast 700fps, 1760x1680 pixels, Visible CMOS Imager and camera development; c) status of and development plans for the Selex SAPHIRA NIR eAPD and controller. Most of the instruments and detector/camera developments are described in more detail in other papers at this conference.
Further evidence for cosmological evolution of the fine structure constant.
Webb, J K; Murphy, M T; Flambaum, V V; Dzuba, V A; Barrow, J D; Churchill, C W; Prochaska, J X; Wolfe, A M
2001-08-27
We describe the results of a search for time variability of the fine structure constant alpha using absorption systems in the spectra of distant quasars. Three large optical data sets and two 21 cm and mm absorption systems provide four independent samples, spanning approximately 23% to 87% of the age of the universe. Each sample yields a smaller alpha in the past and the optical sample shows a 4 sigma deviation: Delta alpha/alpha = -0.72+/-0.18 x 10(-5) over the redshift range 0.5
Conditional Selection of Genomic Alterations Dictates Cancer Evolution and Oncogenic Dependencies.
Mina, Marco; Raynaud, Franck; Tavernari, Daniele; Battistello, Elena; Sungalee, Stephanie; Saghafinia, Sadegh; Laessle, Titouan; Sanchez-Vega, Francisco; Schultz, Nikolaus; Oricchio, Elisa; Ciriello, Giovanni
2017-08-14
Cancer evolves through the emergence and selection of molecular alterations. Cancer genome profiling has revealed that specific events are more or less likely to be co-selected, suggesting that the selection of one event depends on the others. However, the nature of these evolutionary dependencies and their impact remain unclear. Here, we designed SELECT, an algorithmic approach to systematically identify evolutionary dependencies from alteration patterns. By analyzing 6,456 genomes from multiple tumor types, we constructed a map of oncogenic dependencies associated with cellular pathways, transcriptional readouts, and therapeutic response. Finally, modeling of cancer evolution shows that alteration dependencies emerge only under conditional selection. These results provide a framework for the design of strategies to predict cancer progression and therapeutic response. Copyright © 2017 Elsevier Inc. All rights reserved.
Social behavioural epistemology and the scientific community.
Watve, Milind
2017-07-01
The progress of science is influenced substantially by social behaviour of and social interactions within the scientific community. Similar to innovations in primate groups, the social acceptance of an innovation depends not only upon the relevance of the innovation but also on the social dominance and connectedness of the innovator. There are a number of parallels between many well-known phenomena in behavioural evolution and various behavioural traits observed in the scientific community. It would be useful, therefore, to use principles of behavioural evolution as hypotheses to study the social behaviour of the scientific community. I argue in this paper that a systematic study of social behavioural epistemology is likely to boost the progress of science by addressing several prevalent biases and other problems in scientific communication and by facilitating appropriate acceptance/rejection of novel concepts.
The missing link: evolution of the primate cerebellum.
MacLeod, Carol
2012-01-01
The cerebellum has too often been seen as the "little brain," subservient to the "big brain," the cerebrum. That is changing, as neuroimaging uncovers the cerebellum as the "missing link" in the neurological underpinnings of many cognitive domains. Connections between the neocortex and the cerebellum are now more precisely defined, with functionally localized areas of cerebellar cortex understood for cognitive tasks in humans. Comparative volumetric studies of the primate cerebellum have isolated some elements of circuitry, and our field is moving toward a better integration with the neurosciences in a systematic comparative framework. The next decade may show great advances, as relatively noninvasive techniques of neuroimaging have the potential to build a comparative model of the evolution of primate neurocircuitry. Copyright © 2012 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Liang, Xianqing; Pan, Deyou; Lao, Ming; Liang, Shuiying; Huang, Dan; Zhou, Wenzheng; Guo, Jin
2017-05-01
The structural evolution of fluorinated graphene (FG) nanosheets upon molten-alkali treatment has been systematically investigated utilizing X-ray absorption near-edge structure (XANES) spectroscopy. It is found that the hydroxyl groups can progressively displace fluorine atoms to form covalent bonds to the graphene sheets under designed molten-alkali condition. The XANES spectra also reveal the formation of epoxide groups through intramolecular dehydration of neighbouring hydroxyl groups after substitution reaction. At high alkali-FG weight ratio, the restoration of the π-conjugated structure in graphene sheets can be observed due to the gradual decomposition of epoxide groups. Our experimental results indicate that the surface chemistry and electronic structure of hydroxyl-functionalized FG (HFG) can be readily tuned by varying the ratio of reactants.
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.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Margie Jeffs; R. Douglas Hamelin
Integrated Product Development Teams (IPDT) are a key component of any systems engineering (SE) application, but since they are formed primarily from technical considerations, many IPDTs are far less productive than they otherwise could be. By recognizing specific personality types and skill sets, a random group of 'technical' individuals can be structured to become a highly effective team capable of delivering much more than the sum of its members.
The Evolution and Utility of the Burn Specific Health Scale: A Systematic Review
2010-01-01
burn survivors facing substantial long-term rehabilitation and life-long physical, social and psychological challenges. A burn is one of the most...as functional, emotional, and social readjustment [5]. Sudden and serious burn precipitates cognitive and emotional challenges that affect the course...state of complete physical, mental and social well- being and not merely the absence of disease or infirmity’’ [11]. More recently, there is agreement
Sky Luminaries in the Space Orienting Activity of Homo Sapiens in the Middle Palaeolithic
NASA Astrophysics Data System (ADS)
Kaurov, E. N.
Data describing the beginnings of the space orienting activity of Homo sapiens is analysed and systematized: observation of the Pole and the recognition of Ursa Major were used as the basis of the determination of the points of the compass. Data and results from astronomy, history of astronomy, archaeology and palaeoanthropology were used for the reconstruction of the evolution of the space orienting activity of Homo sapiens.
Shoreline Change and Storm-Induced Beach Erosion Modeling: A Collection of Seven Papers
1990-03-01
reducing, and analyzing the data in a systematic manner. Most physical data needed for evaluating and interpreting shoreline and beach evolution processes...proposed development concepts using both physical and numerical models. b. Analyzed and interpreted model results. c. Provided technical documentation of... interpret study results in the context required for "Confirmation" hearings. 26 The Corps of Engineers, Los Angeles District (SPL), has also begun studies
The Evolution of Joint Operations during the Civil War
2009-06-12
requested a large quantity of anti-personnel mines to enhance the minefield in front of the land face.64 Lamb‘s requests did not elicit a significant... mines the Confederates had buried. Several of the men realized what they were (buried anti-personnel torpedoes) and systematically disabled them by...devices which today would include booby traps, land mines , naval mines and others. 118 Traverse--A fortified gun emplacement in a fortified position
Long-Term Evolution of the Electrical Stimulation Levels for Cochlear Implant Patients
Vargas, Jose Luis; Sainz, Manuel; Roldan, Cristina; de la Torre, Angel
2012-01-01
Objectives The stimulation levels programmed in cochlear implant systems are affected by an evolution since the first switch-on of the processor. This study was designed to evaluate the changes in stimulation levels over time and the relationship between post-implantation physiological changes and with the hearing experience provided by the continuous use of the cochlear implant. Methods Sixty-two patients, ranging in age from 4 to 68 years at the moment of implantation participated in this study. All subjects were implanted with the 12 channels COMBI 40+ cochlear implant at San Cecilio University Hospital, Granada, Spain. Hearing loss etiology and progression characteristics varied across subjects. Results The analyzed programming maps show that the stimulation levels suffer a fast evolution during the first weeks after the first switch-on of the processor. Then, the evolution becomes slower and the programming parameters tend to be stable at about 6 months after the first switch-on. The evolution of the stimulation levels implies an increment of the electrical dynamic range, which is increased from 15.4 to 20.7 dB and improves the intensity resolution. A significant increment of the sensitivity to acoustic stimuli is also observed. For some patients, we have also observed transitory changes in the electrode impedances associated to secretory otitis media, which cause important changes in the programming maps. Conclusion We have studied the long-term evolution of the stimulation levels in cochlear implant patients. Our results show the importance of systematic measurements of the electrode impedances before the revision of the programming map. This report also highlights that the evolution of the programming maps is an important factor to be considered in order to determine an adequate calendar fitting of the cochlear implant processor. PMID:23205223
Genome-wide signatures of convergent evolution in echolocating mammals
Parker, Joe; Tsagkogeorga, Georgia; Cotton, James A.; Liu, Yuan; Provero, Paolo; Stupka, Elia; Rossiter, Stephen J.
2013-01-01
Evolution is typically thought to proceed through divergence of genes, proteins, and ultimately phenotypes1-3. However, similar traits might also evolve convergently in unrelated taxa due to similar selection pressures4,5. Adaptive phenotypic convergence is widespread in nature, and recent results from a handful of genes have suggested that this phenomenon is powerful enough to also drive recurrent evolution at the sequence level6-9. Where homoplasious substitutions do occur these have long been considered the result of neutral processes. However, recent studies have demonstrated that adaptive convergent sequence evolution can be detected in vertebrates using statistical methods that model parallel evolution9,10 although the extent to which sequence convergence between genera occurs across genomes is unknown. Here we analyse genomic sequence data in mammals that have independently evolved echolocation and show for the first time that convergence is not a rare process restricted to a handful of loci but is instead widespread, continuously distributed and commonly driven by natural selection acting on a small number of sites per locus. Systematic analyses of convergent sequence evolution in 805,053 amino acids within 2,326 orthologous coding gene sequences compared across 22 mammals (including four new bat genomes) revealed signatures consistent with convergence in nearly 200 loci. Strong and significant support for convergence among bats and the dolphin was seen in numerous genes linked to hearing or deafness, consistent with an involvement in echolocation. Surprisingly we also found convergence in many genes linked to vision: the convergent signal of many sensory genes was robustly correlated with the strength of natural selection. This first attempt to detect genome-wide convergent sequence evolution across divergent taxa reveals the phenomenon to be much more pervasive than previously recognised. PMID:24005325
Toward unbiased determination of the redshift evolution of Lyman-alpha forest clouds
NASA Technical Reports Server (NTRS)
Lu, Limin; Zuo, Lin
1994-01-01
The possibility of using D(sub A), the mean depression of a quasar spectrum due to Ly-alpha forest absorption, to study the number density evolution of the Ly-alpha forest clouds is examined in some detail. Current D(sub A) measurements are made against a continuum that is a power-law extrapolation from the continuum longward of Ly-alpha emission. Compared to the line-counting approach, the D(sub A)-method has the advantage that the D(sub A) measurements are not affected by line-blending effects. However, we find using low-redshift quasar spectra obtained with the Hubble Space Telescope (HST), where the true continuum in the Ly-alpha forest can be estimated fairly reliably because of the much lower density of the Ly-alpha forest lines, that the extrapolated continuum often deviates systematically from the true continuum in the forest region. Such systematic continuum errors introduce large errors in the D(sub A) measurements. The current D(sub A) measurements may also be significantly biased by the possible presence of the Gunn-Peterson absorption. We propose a modification to the existing D(sub A)-method, namely, to measure D(sub A) against a locally established continuum in the Ly-alpha forest. Under conditions that the quasar spectrum has good resolution and S/N to allow for a reliable estimate of the local continuum in the Ly-alpha forest, the modified D(sub A) measurements should be largely free of the systematic uncertainties suffered by the existing D(sub A) measurements. We also introduce a formalism based on the work of Zuo (1993) to simplify the application of the D(sub A)-method(s) to real data. We discuss the merits and limitations of the modified D(sub A)-method, and conclude that it is a useful alternative. Our findings that the extrapolated continuum from longward of Ly-alpha emission often deviates systematically from the true continuum in the Ly-alpha forest present a major problem in the study of the Gunn-Peterson absorption.
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.
Constraining Cosmic Dawn and Cosmological Reionization via the global redshifted 21-cm signal
NASA Astrophysics Data System (ADS)
Singh, Saurabh
2018-01-01
The formation of first stars and consequent thermal evolution in baryons during Cosmic Dawn and the Epoch of Reionization (EoR) is poorly constrained. The 21-cm line transition of neutral hydrogen is one of the richest probes of the astrophysics during this era. The signal has the potential to reveal the nature and timing of the emergence of first stars, first light, and the consequent evolution in thermal and ionization state of the baryons.The detection of the global redshifted 21-cm signal, which represents the mean thermal history of the gas, is challenging since it is extremely faint and seen through orders of magnitude stronger contributions from Galactic and extragalactic foregrounds. Man-made terrestrial Radio Frequency Interference (RFI) and the exacting tolerances required on instrument systematics make the detection even more daunting.The design considerations for a precision spectral radiometer are first listed, and a comparison is made of different radiometer configurations, including short and zero baseline interferometers along with methods to enhance the response. We discuss the relative merits of different methods.We then describe SARAS 2, a spectral radiometer custom-designed for precision measurement of the global 21-cm signal. SARAS 2 has been designed to have a system transfer function and internal systematics – both multiplicative and additive – to be spectrally smooth so as to allow a separation of foregrounds and systematics from plausible and predicted global cosmological 21-cm signals. The algorithms for calibration and RFI mitigation are carefully developed so that they do not introduce spectral features that may confuse the detection of the 21-cm signal.We present the outcomes for cosmology from analysis of 60 hr observing with the radiometer deployed at the Timbaktu Collective in Southern India. The detailed analysis of the data reveals an RMS noise level of 11 mK, without being limited by systematic structures. The likelihood ratios are computed from the data for plausible 21-cm signals predicted by theoretical models. First light with SARAS 2 disfavors the scenario of rapid reionization and also the models in which the first X-ray sources have poor heating efficiency.
Phylogenetics of Lophotrochozoan bHLH Genes and the Evolution of Lineage-Specific Gene Duplicates.
Bao, Yongbo; Xu, Fei; Shimeld, Sebastian M
2017-04-01
The gain and loss of genes encoding transcription factors is of importance to understanding the evolution of gene regulatory complexity. The basic helix-loop-helix (bHLH) genes encode a large superfamily of transcription factors. We systematically classify the bHLH genes from five mollusc, two annelid and one brachiopod genomes, tracing the pattern of bHLH gene evolution across these poorly studied Phyla. In total, 56-88 bHLH genes were identified in each genome, with most identifiable as members of previously described bilaterian families, or of new families we define. Of such families only one, Mesp, appears lost by all these species. Additional duplications have also played a role in the evolution of the bHLH gene repertoire, with many new lophotrochozoan-, mollusc-, bivalve-, or gastropod-specific genes defined. Using a combination of transcriptome mining, RT-PCR, and in situ hybridization we compared the expression of several of these novel genes in tissues and embryos of the molluscs Crassostrea gigas and Patella vulgata, finding both conserved expression and evidence for neofunctionalization. We also map the positions of the genes across these genomes, identifying numerous gene linkages. Some reflect recent paralog divergence by tandem duplication, others are remnants of ancient tandem duplications dating to the lophotrochozoan or bilaterian common ancestors. These data are built into a model of the evolution of bHLH genes in molluscs, showing formidable evolutionary stasis at the family level but considerable within-family diversification by tandem gene duplication. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
Ross, Caitlin; Rychtář, Jan; Rueppell, Olav
2015-03-21
Social organization correlates with longevity across animal taxa. This correlation has been explained by selection for longevity by social evolution. The reverse causality is also conceivable but has not been sufficiently considered. We constructed a simple, spatially structured population model of asexually reproducing individuals to study the effect of temporal life history structuring on the evolution of cooperation. Individuals employed fixed strategies of cooperation or defection towards all neighbours in a basic Prisoner's Dilemma paradigm. Individuals aged and transitioned through different life history stages asynchronously without migration. An individual's death triggered a reproductive event by one immediate neighbour. The specific neighbour was chosen probabilistically according to the cumulative payoff from all local interactions. Varying the duration of pre-reproductive, reproductive, and post-reproductive life history stages, long-term simulations allowed a systematic evaluation of the influence of the duration of these specific life history stages. Our results revealed complex interactions among the effects of the three basic life history stages and the benefit to defect. Overall, a long post-reproductive stage promoted the evolution of cooperation, while a prolonged pre-reproductive stage has a negative effect. In general, the total length of life also increased the probability of the evolution of cooperation. Thus, our specific model suggests that the timing of life history transitions and total duration of life history stages may affect the evolution of cooperative behaviour. We conclude that the causation of the empirically observed association of life expectancy and sociality may be more complex than previously realized. Copyright © 2015 Elsevier Ltd. All rights reserved.
Ross, Caitlin; Rychtář, Jan; Rueppell, Olav
2015-01-01
Social organization correlates with longevity across animal taxa. This correlation has been explained by selection for longevity by social evolution. The reverse causality is also conceivable but has not been sufficiently considered. We constructed a simple, spatially structured population model of asexually reproducing individuals to study the effect of temporal life history structuring on the evolution of cooperation. Individuals employed fixed strategies of cooperation or defection towards all neighbours in a basic Prisoner’s Dilemma paradigm. Individuals aged and transitioned through different life history stages asynchronously without migration. An individual’s death triggered a reproductive event by one immediate neighbour. The specific neighbour was chosen probabilistically according to the cumulative payoff from all local interactions. Varying the duration of pre-reproductive, reproductive, and post-reproductive life history stages, long-term simulations allowed a systematic evaluation of the influence of the duration of these specific life history stages. Our results revealed complex interactions among the effects of the three basic life history stages and the benefit to defect. Overall, a long post-reproductive stage promoted the evolution of cooperation, while a prolonged pre-reproductive stage has a negative effect. In general, the total length of life also increased the probability of the evolution of cooperation. Thus, our specific model suggests that the timing of life history transitions and total duration of life history stages may affect the evolution of cooperative behaviour. We conclude that the causation of the empirically observed association of life expectancy and sociality may be more complex than previously realized. PMID:25637763
NASA Astrophysics Data System (ADS)
Contini, E.; Kang, Xi; Romeo, A. D.; Xia, Q.
2017-03-01
We study the connection between the observed star formation rate-stellar mass (SFR-M *) relation and the evolution of the stellar mass function (SMF) by means of a subhalo abundance matching technique coupled to merger trees extracted from an N-body simulation. Our approach, which considers both galaxy mergers and stellar stripping, is to force the model to match the observed SMF at redshift z> 2, and let it evolve down to the present time according to the observed SFR-M * relation. In this study, we use two different sets of SMFs and two SFR-M * relations: a simple power law and a relation with a mass-dependent slope. Our analysis shows that the evolution of the SMF is more consistent with an SFR-M * relation with a mass-dependent slope, in agreement with predictions from other models of galaxy evolution and recent observations. In order to fully and realistically describe the evolution of the SMF, both mergers and stellar stripping must be considered, and we find that both have almost equal effects on the evolution of SMF at the massive end. Taking into account the systematic uncertainties in the observed data, the high-mass end of the SMF obtained by considering stellar stripping results in good agreement with recent observational data from the Sloan Digital Sky Survey. At {log} {M}* < 11.2, our prediction at z = 0.1 is close to Li & White data, but the high-mass end ({log} {M}* > 11.2) is in better agreement with D’Souza et al. data which account for more massive galaxies.
The Nature of the Arguments for Creationism, Intelligent Design, and Evolution
NASA Astrophysics Data System (ADS)
Barnes, Ralph M.; Church, Rebecca A.; Draznin-Nagy, Samuel
2017-03-01
Seventy-two Internet documents promoting creationism, intelligent design (I.D.), or evolution were selected for analysis. The primary goal of each of the 72 documents was to present arguments for creationism, I.D., or evolution. We first identified all arguments in these documents. Each argument was then coded in terms of both argument type (appeal to authority, appeal to empirical evidence, appeal to reason, etc.) and argument topic (age of earth, mechanism of descent with modification, etc.). We then provided a quantitative summary of each argument type and topic for each of the three positions. Three clear patterns were revealed by the data. First, websites promoting evolution were characterized by a narrow focus on appeals to empirical evidence, whereas websites promoting creationism and I.D. were quite heterogeneous in regards to argument type. Second, websites promoting evolution relied primarily on a small number of empirical examples (e.g., fossils, biogeography, homology, etc.), while websites promoting creationism and I.D. used a far greater range of arguments. Finally, websites promoting evolution were narrowly focused on the topic of descent with modification. In contrast, websites promoting creationism tackled a broad range of topics, while websites promoting I.D. were narrowly focused on the issue of the existence of God. The current study provides a quantitative summary of a systematic content analysis of argument type and topic across a large number of frequently accessed websites dealing with origins. The analysis we have used may prove fruitful in identifying and understanding argumentation trends in scientific writing and pseudo-scientific writing.
Design And Construction Of A Miniaturized Motor Controller For Interplanetary Rover
NASA Astrophysics Data System (ADS)
Lofgren, Henrik; Lijemark, Tomas; Lamoureux, Enrique; Bruhn, Fredrik; Hagstrom, Maria; Hall, Karin; Ljunggren, Anders; Habinc, Sandi; Gruener, Gabriel; Rusconi, Andrea; Boyes, Ben; Wagenbach, Susanne; Poulakis, Pantelis; Kohler, Johan
2011-10-01
ÅAC Microtec AB is leading an international consortium developing a Motion Control Chip (MCC) for the European Space Agency (ESA) under a TRP contract. The team consists of the prime ÅAC (Sweden), Aeroflex Gaisler (Sweden), Centre Suisse d'Electroniqueet de Microtechnique (CSEM, Switzerland), Selex Galileo Italy), Astrium (UK) and DLR Institute of Space Systems (Germany). In order to improve performance of rovers and robotic arms, one solution is to place the controller physically as close as possible to the motors. This reduces the harness and hence saves weight, decreases thermal leakage from the main system body and simplifies the final assembly. Nevertheless, with this approach the constraints on the electronics become more stringent: the assembly has to survive a very wide temperature range as well as vibrations and possibly dust, and at the same time it should be as small and light as possible. To cope with these design constraints, the Motion Control Chip (MCC) is based on stacked ceramic substrate technology in a Multi Chip Module (MCM), on which active components are assembled as bare dies. This approach was chosen in favor of special large ASIC development to reduce cost and make the design more flexible. By choosing a MCM solution, the design will allow both FPGA and ASICs to be used. FPGAs are used initially to lower the prototyping cost and later be replaced with ASICs as the packaging technology is qualified for the extreme environments of ISS, Mars and Moon. The manufacturing of the first iteration of miniaturized MCC modules is ongoing and initial functional tests have been executed. The results are currently being evaluated and when this is finalized the full test campaign including environmental tests will planned in detail. The tests are assumed to be finalized during the spring of 2011. Aeroflex Gaisler is the official ESA maintainer of the RTEMS port for the LEON3 processor and has been providing support to several developments. CSEM is providing the software for the MCC, which includes PID position, velocity, and torque control for brushed and brushless DC motors, as well as telecommand, telemetry and housekeeping through SpaceWire and CAN bus. Astrium UK is in charge of the definition of requirements for rover locomotion applications of the MCC. Astrium UK has experience from the Beagle project and is responsible for the Exomars rover development. Selex Galileo is in charge of the definition of requirements for three major applications of the MCC: robotic arms, complex motorized payloads (as drills and sample distribution systems) and exoskeletons. DLR Institute of Space Systems contributes to the definition of requirements related to rover locomotion drives and is furthermore in charge of environmental testing of the MCC prototype.
Hyperspectral Data Processing and Mapping of Soil Parameters: Preliminary Data from Tuscany (Italy)
NASA Astrophysics Data System (ADS)
Garfagnoli, F.; Moretti, S.; Catani, F.; Innocenti, L.; Chiarantini, L.
2010-12-01
Hyperspectral imaging has become a very powerful remote sensing tool for its capability of performing chemical and physical analysis of the observed areas. The objective of this study is to retrieve and characterize clay mineral content of the cultivated layer of soils, from both airborne hyperspectral and field spectrometry surveys in the 400-2500 nm spectral range. Correlation analysis is used to examine the possibility to predict the selected property using high-resolution reflectance spectra and images. The study area is located in the Mugello basin, about 30 km north of Firenze (Tuscany, Italy). Agriculturally suitable terrains are assigned mainly to annual crops, marginally to olive groves, vineyards and orchards. Soils mostly belong to Regosols and Cambisols orders. About 80 topsoil samples scattered all over the area were collected simultaneously with the flight of SIM.GA hyperspectral camera from Selex Galileo. The quantitative determination of clay minerals content in soil samples was performed by means of XRD and Rietveld refinement. An ASD FieldSpec spectroradiometer was used to obtain reflectance spectra from dried, crushed and sieved samples under controlled laboratory conditions. Different chemometric techniques (multiple linear regression, vertex component analysis, partial least squares regression and band depth analysis) were preliminarily tested to correlate mineralogical records with reflectance data. A one component partial least squares regression model yielded a preliminary R2 value of 0.65. A similar result was achieved by plotting the absorption peak depth at 2210 versus total clay mineral content (band-depth analysis). A complete hyperspectral geocoded reflectance dataset was collected using SIM.GA hyperspectral image sensor from Selex-Galileo, mounted on board of the University of Firenze ultra light aircraft. The approximate pixel resolution was 0.6 m (VNIR) and 1.2 m (SWIR). Airborne SIM.GA row data were firstly transformed into at-sensor radiance values, where calibration coefficients and parameters from laboratory measurements are applied to non-georeferred VNIR/SWIR DN values. Then, geocoded products are retrieved for each flight line by using a procedure developed in IDL Language and PARGE (PARametric Geocoding) software. When all compensation parameters are applied to hyperspectral data or to the final thematic map, orthorectified, georeferred and coregistered VNIR to SWIR images or maps are available for GIS application and 3D view. Airborne imagery has to be corrected for the influence of the atmosphere, solar illumination, sensor viewing geometry and terrain geometry information, for the retrieval of inherent surface reflectance properties. Then, different geophysical parameters can be investigated and retrieved by means of inversion algorithms. The experimental fitting of laboratory data on mineral content is used for airborne data inversion, whose results are in agreement with laboratory records, demonstrating the possibility to use this methodology for digital mapping of soil properties.
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).
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.
Versatility and Invariance in the Evolution of Homologous Heteromeric Interfaces
Andreani, Jessica; Faure, Guilhem; Guerois, Raphaël
2012-01-01
Evolutionary pressures act on protein complex interfaces so that they preserve their complementarity. Nonetheless, the elementary interactions which compose the interface are highly versatile throughout evolution. Understanding and characterizing interface plasticity across evolution is a fundamental issue which could provide new insights into protein-protein interaction prediction. Using a database of 1,024 couples of close and remote heteromeric structural interologs, we studied protein-protein interactions from a structural and evolutionary point of view. We systematically and quantitatively analyzed the conservation of different types of interface contacts. Our study highlights astonishing plasticity regarding polar contacts at complex interfaces. It also reveals that up to a quarter of the residues switch out of the interface when comparing two homologous complexes. Despite such versatility, we identify two important interface descriptors which correlate with an increased conservation in the evolution of interfaces: apolar patches and contacts surrounding anchor residues. These observations hold true even when restricting the dataset to transiently formed complexes. We show that a combination of six features related either to sequence or to geometric properties of interfaces can be used to rank positions likely to share similar contacts between two interologs. Altogether, our analysis provides important tracks for extracting meaningful information from multiple sequence alignments of conserved binding partners and for discriminating near-native interfaces using evolutionary information. PMID:22952442
Use of the "Tree" Analogy in Evolution Teaching by Biology Teachers
NASA Astrophysics Data System (ADS)
Marcelos, Maria Fátima; Nagem, Ronaldo Luiz
2012-04-01
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 text or other analogies between the tree and evolution, and whether they adopt a specific methodology for teaching with analogies and metaphors (A&M). The academic training of teachers regarding use of A&M is review briefly. A diagnostic study was carried out with biology teachers in a public school in the town of Contagem in the state of Minas Gerais in Brazil. The data were obtained through direct observation, questionnaires and a focus group. The teachers pointed out in the questionnaires that some details of Darwin's analogy are utilized as a resource. However, analysis of the data indicates that the `Tree of Life' text is not known or utilized in class. At the same time, the teachers state that they use aspects of the tree as a didactic resource to teach evolution and that its use facilitates the learning of content. The teachers have little knowledge of specific methodologies of teaching with analogies and metaphors, revealing that their training is incomplete in this area.
Koskella, Britt; Taylor, Tiffany B; Bates, Jennifer; Buckling, Angus
2011-01-01
Resistance of bacteria to phages may be gained by alteration of surface proteins to which phages bind, a mechanism that is likely to be costly as these molecules typically have critical functions such as movement or nutrient uptake. To address this potential trade-off, we combine a systematic study of natural bacteria and phage populations with an experimental evolution approach. We compare motility, growth rate and susceptibility to local phages for 80 bacteria isolated from horse chestnut leaves and, contrary to expectation, find no negative association between resistance to phages and bacterial motility or growth rate. However, because correlational patterns (and their absence) are open to numerous interpretations, we test for any causal association between resistance to phages and bacterial motility using experimental evolution of a subset of bacteria in both the presence and absence of naturally associated phages. Again, we find no clear link between the acquisition of resistance and bacterial motility, suggesting that for these natural bacterial populations, phage-mediated selection is unlikely to shape bacterial motility, a key fitness trait for many bacteria in the phyllosphere. The agreement between the observed natural pattern and the experimental evolution results presented here demonstrates the power of this combined approach for testing evolutionary trade-offs. PMID:21509046
Linkage of A-to-I RNA Editing in Metazoans and the Impact on Genome Evolution
Duan, Yuange; Dou, Shengqian; Zhang, Hong; Wu, Changcheng; Wu, Mingming
2018-01-01
Abstract The adenosine-to-inosine (A-to-I) RNA editomes have been systematically characterized in various metazoan species, and many editing sites were found in clusters. However, it remains unclear whether the clustered editing sites tend to be linked in the same RNA molecules or not. By adopting a method originally designed to detect linkage disequilibrium of DNA mutations, we examined the editomes of ten metazoan species and detected extensive linkage of editing in Drosophila and cephalopods. The prevalent linkages of editing in these two clades, many of which are conserved between closely related species and might be associated with the adaptive proteomic recoding, are maintained by natural selection at the cost of genome evolution. Nevertheless, in worms and humans, we only detected modest proportions of linked editing events, the majority of which were not conserved. Furthermore, the linkage of editing in coding regions of worms and humans might be overall deleterious, which drives the evolution of DNA sites to escape promiscuous editing. Altogether, our results suggest that the linkage landscape of A-to-I editing has evolved during metazoan evolution. This present study also suggests that linkage of editing should be considered in elucidating the functional consequences of RNA editing. PMID:29048557
Wind-tunnel modelling of the tip-speed ratio influence on the wake evolution
NASA Astrophysics Data System (ADS)
Stein, Victor P.; Kaltenbach, Hans-Jakob
2016-09-01
Wind-tunnel measurements on the near-wake evolution of a three bladed horizontal axis wind turbine model (HAWT) in the scale 1:O(350) operating in uniform flow conditions and within a turbulent boundary layer at different tip speed ratios are presented. Operational conditions are chosen to exclude Reynolds number effects regarding the turbulent boundary layer as well as the rotor performance. Triple-wire anemometry is used to measure all three velocity components in the mid-vertical and mid-horizontal plane, covering the range from the near- to the far-wake region. In order to analyse wake properties systematically, power and thrust coefficients of the turbine were measured additionally. It is confirmed that realistic modelling of the wake evolution is not possible in a low-turbulence uniform approach flow. Profiles of mean velocity and turbulence intensity exhibit large deviations between the low-turbulence uniform flow and the turbulent boundary layer, especially in the far-wake region. For nearly constant thrust coefficients differences in the evolution of the near-wake can be identified for tip speed ratios in the range from 6.5 to 10.5. It is shown that with increasing downstream distances mean velocity profiles become indistinguishable whereas for turbulence statistics a subtle dependency on the tip speed ratio is still noticeable in the far-wake region.
NASA Astrophysics Data System (ADS)
Gurao, N. P.; Suwas, Satyam
2017-02-01
Deformation texture evolution in two-phase xFe- yNi-(100- x- y)Cr model alloys and Ti-13Nb-13Zr alloy was studied during rolling to develop an understanding of micro-mechanisms of deformation in industrially relevant two-phase FCC-BCC steels and HCP-BCC titanium alloys, respectively. It was found that volume fraction and contiguity of phases lead to systematic changes in texture, while morphology affects the strength of texture. There was a characteristic change in texture from typical Brass-type to a weaker Copper-type texture in the austenite phase accompanied with a change from alpha fiber to gamma fiber in ferrite phase for Fe-Ni-Cr alloys with increase in fraction of harder ferrite phase. However, similar characteristic texture evolution was noted in both α and β phase irrespective of the different initial morphologies in Ti-13Nb-13Zr alloy. Viscoplastic self-consistent simulations with two-phase scheme were able to qualitatively predict texture evolution in individual phases. It is proposed that the transition from iso-strain-type behavior for equiaxed microstructure at low strain to iso-stress-type behavior at higher strain is aided by the presence of higher volume fraction of the second phase and increasing aspect ratio of individual phases in two-phase alloys.
Parental effects and the evolution of phenotypic memory.
Kuijper, B; Johnstone, R A
2016-02-01
Despite growing evidence for nongenetic inheritance, the ecological conditions that favour the evolution of heritable parental or grandparental effects remain poorly understood. Here, we systematically explore the evolution of parental effects in a patch-structured population with locally changing environments. When selection favours the production of a mix of offspring types, this mix differs according to the parental phenotype, implying that parental effects are favoured over selection for bet-hedging in which the mixture of offspring phenotypes produced does not depend on the parental phenotype. Positive parental effects (generating a positive correlation between parental and offspring phenotype) are favoured in relatively stable habitats and when different types of local environment are roughly equally abundant, and can give rise to long-term parental inheritance of phenotypes. By contrast, unstable habitats can favour negative parental effects (generating a negative correlation between parental and offspring phenotype), and under these circumstances, even slight asymmetries in the abundance of local environmental states select for marked asymmetries in transmission fidelity. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.
Core–Shell Au@Metal-Oxide Nanoparticle Electrocatalysts for Enhanced Oxygen Evolution
Strickler, Alaina L.; Escudero-Escribano, Marı́a; Jaramillo, Thomas F.
2017-09-25
Enhanced catalysis for electrochemical oxygen evolution is essential for the efficacy of many renewable energy technologies, including water electrolyzers and metal–air batteries. Recently, Au supports have been shown to enhance the activity of many 3d transition metal-oxide thin films for the oxygen evolution reaction (OER) in alkaline media. In this paper, we translate the beneficial impact of Au supports to high surface area, device-ready core–shell nanoparticles consisting of a Au-core and a metal-oxide shell (Au@M xO y where M = Ni, Co, Fe, and CoFe). Through a systematic evaluation, we establish trends in performance and illustrate the universal activity enhancementmore » when employing the Au-core in the 3d transition metal-oxide nanoparticles. Finally, the highest activity particles, Au@CoFeO x, demonstrate an overpotential of 328 ± 3 mV over a 2 h stability test at 10 mA cm –2, illustrating that strategically coupling Au support and mixed metal-oxide effects in a core–shell nanoparticle morphology is a promising avenue to achieve device-ready, high-performance OER catalysts.« less
Arnoldt, Hinrich; Strogatz, Steven H; Timme, Marc
2015-01-01
It has been hypothesized that in the era just before the last universal common ancestor emerged, life on earth was fundamentally collective. Ancient life forms shared their genetic material freely through massive horizontal gene transfer (HGT). At a certain point, however, life made a transition to the modern era of individuality and vertical descent. Here we present a minimal model for stochastic processes potentially contributing to this hypothesized "Darwinian transition." The model suggests that HGT-dominated dynamics may have been intermittently interrupted by selection-driven processes during which genotypes became fitter and decreased their inclination toward HGT. Stochastic switching in the population dynamics with three-point (hypernetwork) interactions may have destabilized the HGT-dominated collective state and essentially contributed to the emergence of vertical descent and the first well-defined species in early evolution. A systematic nonlinear analysis of the stochastic model dynamics covering key features of evolutionary processes (such as selection, mutation, drift and HGT) supports this view. Our findings thus suggest a viable direction out of early collective evolution, potentially enabling the start of individuality and vertical Darwinian evolution.
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.
Just enough inflation: power spectrum modifications at large scales
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cicoli, Michele; Downes, Sean; Dutta, Bhaskar
2014-12-01
We show that models of 'just enough' inflation, where the slow-roll evolution lasted only 50- 60 e-foldings, feature modifications of the CMB power spectrum at large angular scales. We perform a systematic analytic analysis in the limit of a sudden transition between any possible non-slow-roll background evolution and the final stage of slow-roll inflation. We find a high degree of universality since most common backgrounds like fast-roll evolution, matter or radiation-dominance give rise to a power loss at large angular scales and a peak together with an oscillatory behaviour at scales around the value of the Hubble parameter at themore » beginning of slow-roll inflation. Depending on the value of the equation of state parameter, different pre-inflationary epochs lead instead to an enhancement of power at low ℓ, and so seem disfavoured by recent observational hints for a lack of CMB power at ℓ∼< 40. We also comment on the importance of initial conditions and the possibility to have multiple pre-inflationary stages.« less
Core–Shell Au@Metal-Oxide Nanoparticle Electrocatalysts for Enhanced Oxygen Evolution
DOE Office of Scientific and Technical Information (OSTI.GOV)
Strickler, Alaina L.; Escudero-Escribano, Marı́a; Jaramillo, Thomas F.
Enhanced catalysis for electrochemical oxygen evolution is essential for the efficacy of many renewable energy technologies, including water electrolyzers and metal–air batteries. Recently, Au supports have been shown to enhance the activity of many 3d transition metal-oxide thin films for the oxygen evolution reaction (OER) in alkaline media. In this paper, we translate the beneficial impact of Au supports to high surface area, device-ready core–shell nanoparticles consisting of a Au-core and a metal-oxide shell (Au@M xO y where M = Ni, Co, Fe, and CoFe). Through a systematic evaluation, we establish trends in performance and illustrate the universal activity enhancementmore » when employing the Au-core in the 3d transition metal-oxide nanoparticles. Finally, the highest activity particles, Au@CoFeO x, demonstrate an overpotential of 328 ± 3 mV over a 2 h stability test at 10 mA cm –2, illustrating that strategically coupling Au support and mixed metal-oxide effects in a core–shell nanoparticle morphology is a promising avenue to achieve device-ready, high-performance OER catalysts.« less
Evolution of the central safety factor during stabilized sawtooth instabilities at KSTAR
NASA Astrophysics Data System (ADS)
Messmer, M. C. C.; Ko, J.; Chung, J.; Woo, M. H.; Lee, K.-D.; Jaspers, R. J. E.
2018-01-01
A motional Stark effect (MSE) diagnostic has recently been installed in the KSTAR tokamak. A difficulty faced at KSTAR and common to other MSE diagnostics is calibration of the system for absolute measurements. In this report we present our novel calibration routine and discuss first results, evaluating the evolution of the the central safety factor during sawtooth instabilities. The calibration scheme ensures that the bandpass filters typically used in MSE systems are aligned correctly and identifies and removes systematic offsets present in the measurement. This is verified by comparing the reconstructed safety factor profile against various discharges where the locations of rational q surfaces have been obtained from MHD markers. The calibration is applied to analyse the evolution of q 0 in a shot where the sawteeth are stabilized by neutral beam injection. Within the analysed sawtooth periods q 0 drops below unity during the quiescent phase and relaxes close to or slightly above unity at the sawtooth crash. This finding is in line with the classical Kadomtsev model of full magnetic reconnection and earlier findings at JET.
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.
Fossil evidence for the early ant evolution
NASA Astrophysics Data System (ADS)
Perrichot, Vincent; Lacau, Sébastien; Néraudeau, Didier; Nel, André
2008-02-01
Ants are one of the most studied insects in the world; and the literature devoted to their origin and evolution, systematics, ecology, or interactions with plants, fungi and other organisms is prolific. However, no consensus yet exists on the age estimate of the first Formicidae or on the origin of their eusociality. We review the fossil and biogeographical record of all known Cretaceous ants. We discuss the possible origin of the Formicidae with emphasis on the most primitive subfamily Sphecomyrminae according to its distribution and the Early Cretaceous palaeogeography. And we review the evidence of true castes and eusociality of the early ants regarding their morphological features and their manner of preservation in amber. The mid-Cretaceous amber forest from south-western France where some of the oldest known ants lived, corresponded to a moist tropical forest close to the shore with a dominance of gymnosperm trees but where angiosperms (flowering plants) were already diversified. This palaeoenvironmental reconstruction supports an initial radiation of ants in forest ground litter coincident with the rise of angiosperms, as recently proposed as an ecological explanation for their origin and successful evolution.
Injection initiated fracture in soft solids
NASA Astrophysics Data System (ADS)
Hutchens, Shelby; Yang, Steven
Damage accumulation in soft materials under hydrostatic loading conditions is a primary injury mechanism in blast and blunt force trauma. A recently explored technique known as cavitation rheology (CR) provides a promising avenue for quickly and inexpensively approximating hydrostatic conditions via the reverse loading scenario, void pressurization. Past CR measurements of synthetic, polymeric materials at length scales from mm's to μm's have been found to correlate with both elastic modulus and fracture energy. The technique is performed via pressurization of fluid within a needle that is embedded within a material. This experimental setup allows crack evolution to be monitored, similar to traditional pre-notched failure samples. We observe a systematic evolution of crack morphology as a function of cross-link density in a soft elastomer. Crack shape is quantified using micro-computed tomography and shown to transition from being roughly penny-shaped to multi-lobed (predominately three) to spherical with decreasing crosslinking. Moduli are on the order of kPa. We describe this morphology evolution using a balance between the energetic costs of the strain energy in deforming the surrounding material and the intrinsic fracture energy necessary to form a new surface.
The taxonomy, biology and chemistry of the fungal Pestalotiopsis genus.
Yang, Xiao-Long; Zhang, Jing-Ze; Luo, Du-Qiang
2012-06-01
A growing body of evidence indicates that the Pestalotiopsis genus represents a huge and largely untapped resource of natural products with chemical structures that have been optimized by evolution for biological and ecological relevance. So far, 196 secondary metabolites have been encountered in this genus. This review systematically surveys the taxonomy, biology and chemistry of the Pestalotiopsis genus. It also summarises the biosynthetic relationships and chemical synthesis of metabolites from this genus. There are 184 references.
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
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.
Galaxy-galaxy lensing in the Dark Energy Survey Science Verification data
Clampitt, J.; S?nchez, C.; Kwan, J.; ...
2016-11-22
We present galaxy-galaxy lensing results from 139 square degrees of Dark Energy Survey (DES) Science Verification (SV) data. Our lens sample consists of red galaxies, known as redMaGiC, which are specifically selected to have a low photometric redshift error and outlier rate. The lensing measurement has a total signal-to-noise of 29 over scales $0.09 < R < 15$ Mpc/$h$, including all lenses over a wide redshift range $0.2 < z < 0.8$. Dividing the lenses into three redshift bins for this constant moving number density sample, we find no evidence for evolution in the halo mass with redshift. We obtainmore » consistent results for the lensing measurement with two independent shear pipelines, ngmix and im3shape. We perform a number of null tests on the shear and photometric redshift catalogs and quantify resulting systematic uncertainties. Covariances from jackknife subsamples of the data are validated with a suite of 50 mock surveys. The results and systematics checks in this work provide a critical input for future cosmological and galaxy evolution studies with the DES data and redMaGiC galaxy samples. We fit a Halo Occupation Distribution (HOD) model, and demonstrate that our data constrains the mean halo mass of the lens galaxies, despite strong degeneracies between individual HOD parameters.« less
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.
Galaxy-galaxy lensing in the Dark Energy Survey Science Verification data
DOE Office of Scientific and Technical Information (OSTI.GOV)
Clampitt, J.; S?nchez, C.; Kwan, J.
We present galaxy-galaxy lensing results from 139 square degrees of Dark Energy Survey (DES) Science Verification (SV) data. Our lens sample consists of red galaxies, known as redMaGiC, which are specifically selected to have a low photometric redshift error and outlier rate. The lensing measurement has a total signal-to-noise of 29 over scales $0.09 < R < 15$ Mpc/$h$, including all lenses over a wide redshift range $0.2 < z < 0.8$. Dividing the lenses into three redshift bins for this constant moving number density sample, we find no evidence for evolution in the halo mass with redshift. We obtainmore » consistent results for the lensing measurement with two independent shear pipelines, ngmix and im3shape. We perform a number of null tests on the shear and photometric redshift catalogs and quantify resulting systematic uncertainties. Covariances from jackknife subsamples of the data are validated with a suite of 50 mock surveys. The results and systematics checks in this work provide a critical input for future cosmological and galaxy evolution studies with the DES data and redMaGiC galaxy samples. We fit a Halo Occupation Distribution (HOD) model, and demonstrate that our data constrains the mean halo mass of the lens galaxies, despite strong degeneracies between individual HOD parameters.« less
Prokaryotic evolution and the tree of life are two different things
Bapteste, Eric; O'Malley, Maureen A; Beiko, Robert G; Ereshefsky, Marc; Gogarten, J Peter; Franklin-Hall, Laura; Lapointe, François-Joseph; Dupré, John; Dagan, Tal; Boucher, Yan; Martin, William
2009-01-01
Background The concept of a tree of life is prevalent in the evolutionary literature. It stems from attempting to obtain a grand unified natural system that reflects a recurrent process of species and lineage splittings for all forms of life. Traditionally, the discipline of systematics operates in a similar hierarchy of bifurcating (sometimes multifurcating) categories. The assumption of a universal tree of life hinges upon the process of evolution being tree-like throughout all forms of life and all of biological time. In multicellular eukaryotes, the molecular mechanisms and species-level population genetics of variation do indeed mainly cause a tree-like structure over time. In prokaryotes, they do not. Prokaryotic evolution and the tree of life are two different things, and we need to treat them as such, rather than extrapolating from macroscopic life to prokaryotes. In the following we will consider this circumstance from philosophical, scientific, and epistemological perspectives, surmising that phylogeny opted for a single model as a holdover from the Modern Synthesis of evolution. Results It was far easier to envision and defend the concept of a universal tree of life before we had data from genomes. But the belief that prokaryotes are related by such a tree has now become stronger than the data to support it. The monistic concept of a single universal tree of life appears, in the face of genome data, increasingly obsolete. This traditional model to describe evolution is no longer the most scientifically productive position to hold, because of the plurality of evolutionary patterns and mechanisms involved. Forcing a single bifurcating scheme onto prokaryotic evolution disregards the non-tree-like nature of natural variation among prokaryotes and accounts for only a minority of observations from genomes. Conclusion Prokaryotic evolution and the tree of life are two different things. Hence we will briefly set out alternative models to the tree of life to study their evolution. Ultimately, the plurality of evolutionary patterns and mechanisms involved, such as the discontinuity of the process of evolution across the prokaryote-eukaryote divide, summons forth a pluralistic approach to studying evolution. Reviewers This article was reviewed by Ford Doolittle, John Logsdon and Nicolas Galtier. PMID:19788731
Prokaryotic evolution and the tree of life are two different things.
Bapteste, Eric; O'Malley, Maureen A; Beiko, Robert G; Ereshefsky, Marc; Gogarten, J Peter; Franklin-Hall, Laura; Lapointe, François-Joseph; Dupré, John; Dagan, Tal; Boucher, Yan; Martin, William
2009-09-29
The concept of a tree of life is prevalent in the evolutionary literature. It stems from attempting to obtain a grand unified natural system that reflects a recurrent process of species and lineage splittings for all forms of life. Traditionally, the discipline of systematics operates in a similar hierarchy of bifurcating (sometimes multifurcating) categories. The assumption of a universal tree of life hinges upon the process of evolution being tree-like throughout all forms of life and all of biological time. In multicellular eukaryotes, the molecular mechanisms and species-level population genetics of variation do indeed mainly cause a tree-like structure over time. In prokaryotes, they do not. Prokaryotic evolution and the tree of life are two different things, and we need to treat them as such, rather than extrapolating from macroscopic life to prokaryotes. In the following we will consider this circumstance from philosophical, scientific, and epistemological perspectives, surmising that phylogeny opted for a single model as a holdover from the Modern Synthesis of evolution. It was far easier to envision and defend the concept of a universal tree of life before we had data from genomes. But the belief that prokaryotes are related by such a tree has now become stronger than the data to support it. The monistic concept of a single universal tree of life appears, in the face of genome data, increasingly obsolete. This traditional model to describe evolution is no longer the most scientifically productive position to hold, because of the plurality of evolutionary patterns and mechanisms involved. Forcing a single bifurcating scheme onto prokaryotic evolution disregards the non-tree-like nature of natural variation among prokaryotes and accounts for only a minority of observations from genomes. Prokaryotic evolution and the tree of life are two different things. Hence we will briefly set out alternative models to the tree of life to study their evolution. Ultimately, the plurality of evolutionary patterns and mechanisms involved, such as the discontinuity of the process of evolution across the prokaryote-eukaryote divide, summons forth a pluralistic approach to studying evolution. This article was reviewed by Ford Doolittle, John Logsdon and Nicolas Galtier.
[Planning With Nanda, Noc, Nic Taxonomies In Neurologic Rehabilitation. A clinical study].
Iori, Alessandra; Foracchia, Marco; Gradellini, Cinzia
2015-01-01
Nursing classifications identify a specific professional responsibility, increase nursing visibility, according with nursing evolution of these last years. To evaluate care planning with NANDA taxonomy in neurologic rehabilitation context. Care plan managing with NANDA taxonomy, regarding diagnosis of constipation and impaired skin integrity, using a computerized tool for systematically observation, organized in check list. Registered data with taxonomy planning are higher in quantitative and qualitative terms. For most of patients (87%) one diagnosis has been opened, both diagnosis for 60% of them. Nursing care plan with NANDA taxonomy can be considered a valid methodology of care for neurologic patient, this since it requests a deep and complete registration of first assessment a systematically registration of each monitoring, it increases visibility of nursing job, and it underlines specific autonomy and responsibility in prevention and management of problems.
Interplay between Chaperones and Protein Disorder Promotes the Evolution of Protein Networks
Pechmann, Sebastian; Frydman, Judith
2014-01-01
Evolution is driven by mutations, which lead to new protein functions but come at a cost to protein stability. Non-conservative substitutions are of interest in this regard because they may most profoundly affect both function and stability. Accordingly, organisms must balance the benefit of accepting advantageous substitutions with the possible cost of deleterious effects on protein folding and stability. We here examine factors that systematically promote non-conservative mutations at the proteome level. Intrinsically disordered regions in proteins play pivotal roles in protein interactions, but many questions regarding their evolution remain unanswered. Similarly, whether and how molecular chaperones, which have been shown to buffer destabilizing mutations in individual proteins, generally provide robustness during proteome evolution remains unclear. To this end, we introduce an evolutionary parameter λ that directly estimates the rate of non-conservative substitutions. Our analysis of λ in Escherichia coli, Saccharomyces cerevisiae, and Homo sapiens sequences reveals how co- and post-translationally acting chaperones differentially promote non-conservative substitutions in their substrates, likely through buffering of their destabilizing effects. We further find that λ serves well to quantify the evolution of intrinsically disordered proteins even though the unstructured, thus generally variable regions in proteins are often flanked by very conserved sequences. Crucially, we show that both intrinsically disordered proteins and highly re-wired proteins in protein interaction networks, which have evolved new interactions and functions, exhibit a higher λ at the expense of enhanced chaperone assistance. Our findings thus highlight an intricate interplay of molecular chaperones and protein disorder in the evolvability of protein networks. Our results illuminate the role of chaperones in enabling protein evolution, and underline the importance of the cellular context and integrated approaches for understanding proteome evolution. We feel that the development of λ may be a valuable addition to the toolbox applied to understand the molecular basis of evolution. PMID:24968255
[Historic and functional biology: the inadequacy of a system theory of evolution].
Regelmann, J P
1982-01-01
In the first half of the 20th century neo-Kantianism in a broad sense proved itself the main conceptual and methodological background of the central European biology. As such it contributed much to the victory on the typological, idealistic-morphological and psycho-vitalistic interpretations of life. On the other hand it could not give tools to the biologists for working out a strictly darwinian evolution theory. Kant's theory of organism was conceived without evolution as a theory of the internal functionality of the organism. There was only some 'play' with the evolutionary differentiation of the species. Since then the disputes around the work of August Weismann, a synthetical evolution theory which is now behind time, arose. This theory developed from coinciding claims, elaborated by geneticists, mathematicians, and by biologists studying development, natural history and systematics. This was done under a strong influence of marxist ideas. Through the interweaving of such different approaches it was possible for this evolutionary synthesis to influence successfully the development of evolution research during more than 40 years. Philosophically speaking modern evolution theory means therefore an aversion, even a positive abolition of Kantian positions. A number of biologists however--as L. von Bertalanffy--refused to adhere to a misinterpreted Kantian methodology and oriented themselves to an approach via system theory, which obtained a place in evolution research. In fact this is a Kantian approach as well. They only repeated the Kantian dilemma of the evolution which can also be found in Lamarck and Hegel. The system theory of the functionality of the organism never reaches to the level of the evolving species, but remains always on the level of epigenetic thinking, because of its philosophical origin. This paper points out the consequences of this still current dilemma. At the same time an all-enclosing reflection on the methodological, epistemological and the important historical questions of evolutionary biology in its scientific context is recommended.
Yi, Minhan; Chen, Feng; Luo, Majing; Cheng, Yibin; Zhao, Huabin; Cheng, Hanhua; Zhou, Rongjia
2014-05-19
The Piwi-interacting RNA (piRNA) pathway is responsible for germline specification, gametogenesis, transposon silencing, and genome integrity. Transposable elements can disrupt genome and its functions. However, piRNA pathway evolution and its adaptation to transposon diversity in the teleost fish remain unknown. This article unveils evolutionary scene of piRNA pathway and its association with diverse transposons by systematically comparative analysis on diverse teleost fish genomes. Selective pressure analysis on piRNA pathway and miRNA/siRNA (microRNA/small interfering RNA) pathway genes between teleosts and mammals showed an accelerated evolution of piRNA pathway genes in the teleost lineages, and positive selection on functional PAZ (Piwi/Ago/Zwille) and Tudor domains involved in the Piwi-piRNA/Tudor interaction, suggesting that the amino acid substitutions are adaptive to their functions in piRNA pathway in the teleost fish species. Notably five piRNA pathway genes evolved faster in the swamp eel, a kind of protogynous hermaphrodite fish, than the other teleosts, indicating a differential evolution of piRNA pathway between the swamp eel and other gonochoristic fishes. In addition, genome-wide analysis showed higher diversity of transposons in the teleost fish species compared with mammals. Our results suggest that rapidly evolved piRNA pathway in the teleost fish is likely to be involved in the adaption to transposon diversity. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
Evolution of the social network of scientific collaborations
NASA Astrophysics Data System (ADS)
Barabási, A. L.; Jeong, H.; Néda, Z.; Ravasz, E.; Schubert, A.; Vicsek, T.
2002-08-01
The co-authorship network of scientists represents a prototype of complex evolving networks. In addition, it offers one of the most extensive database to date on social networks. By mapping the electronic database containing all relevant journals in mathematics and neuro-science for an 8-year period (1991-98), we infer the dynamic and the structural mechanisms that govern the evolution and topology of this complex system. Three complementary approaches allow us to obtain a detailed characterization. First, empirical measurements allow us to uncover the topological measures that characterize the network at a given moment, as well as the time evolution of these quantities. The results indicate that the network is scale-free, and that the network evolution is governed by preferential attachment, affecting both internal and external links. However, in contrast with most model predictions the average degree increases in time, and the node separation decreases. Second, we propose a simple model that captures the network's time evolution. In some limits the model can be solved analytically, predicting a two-regime scaling in agreement with the measurements. Third, numerical simulations are used to uncover the behavior of quantities that could not be predicted analytically. The combined numerical and analytical results underline the important role internal links play in determining the observed scaling behavior and network topology. The results and methodologies developed in the context of the co-authorship network could be useful for a systematic study of other complex evolving networks as well, such as the world wide web, Internet, or other social networks.
Irreversible Processes in Ionized Gases
DOE Office of Scientific and Technical Information (OSTI.GOV)
Balescu, R.
1960-01-01
The general theory of irreversible processes, developed by Prigogine and Balescu, is applied to the case of long range interactions in ionized gases. A similar diagram technique permits the systematic selection of all the contributions to the evolution of the distribution function, a an order of approximation equivalent to Debye's equilibrium theory. The infinite series which appear in this way can be summed exactly. The resulting evolution equations have a clear physical significance: they describe interactions of "quasi particles," which are electrons or ions "dressed" by their polarization clouds. These clouds are not a permanent feature, as in equilibrium theory,more » but have a nonequilibrium, changing shape, distorted by the motions of the particles. From the mathematical point of view, these equations exhibit a new type of nonlinearity, which is very directly related to the collective nature of the interactions.« less
Testing market informational efficiency of Constanta port operators
NASA Astrophysics Data System (ADS)
Roşca, E.; Popa, M.; Ruscă, F.; Burciu, Ş.
2015-11-01
The Romanian capital market is still an emergent one. Following the mass- privatization process and the private investments, three of the most important handling and storage companies acting in Constantza Port (OIL Terminal, Comvex and SOCEP) are listed on Romanian Stock Exchange. The paper investigates their evolution on the market, identifying the expected rate of return and the components of the shares risk (specific and systematic). Also, the price evolution could be analyzed through the informational efficiency which instantly reflects the price relevance. The Jarque-Bera normality test regarding the shares return rate distribution and the Fama test for the informational efficiency are completed for each company. The market price model is taken into consideration for price forecasting, computing the return rate auto-correlations. The results are subject of interpretation considering additional managerial and financial information of the companies’ activity.