Mistranslation: from adaptations to applications.

PubMed

Hoffman, Kyle S; O'Donoghue, Patrick; Brandl, Christopher J

2017-11-01

The conservation of the genetic code indicates that there was a single origin, but like all genetic material, the cell's interpretation of the code is subject to evolutionary pressure. Single nucleotide variations in tRNA sequences can modulate codon assignments by altering codon-anticodon pairing or tRNA charging. Either can increase translation errors and even change the code. The frozen accident hypothesis argued that changes to the code would destabilize the proteome and reduce fitness. In studies of model organisms, mistranslation often acts as an adaptive response. These studies reveal evolutionary conserved mechanisms to maintain proteostasis even during high rates of mistranslation. This review discusses the evolutionary basis of altered genetic codes, how mistranslation is identified, and how deviations to the genetic code are exploited. We revisit early discoveries of genetic code deviations and provide examples of adaptive mistranslation events in nature. Lastly, we highlight innovations in synthetic biology to expand the genetic code. The genetic code is still evolving. Mistranslation increases proteomic diversity that enables cells to survive stress conditions or suppress a deleterious allele. Genetic code variants have been identified by genome and metagenome sequence analyses, suppressor genetics, and biochemical characterization. Understanding the mechanisms of translation and genetic code deviations enables the design of new codes to produce novel proteins. Engineering the translation machinery and expanding the genetic code to incorporate non-canonical amino acids are valuable tools in synthetic biology that are impacting biomedical research. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2017 Elsevier B.V. All rights reserved.

Trace Replay and Network Simulation Tool

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

Acun, Bilge; Jain, Nikhil; Bhatele, Abhinav

2015-03-23

TraceR is a trace reply tool built upon the ROSS-based CODES simulation framework. TraceR can be used for predicting network performances and understanding network behavior by simulating messaging in High Performance Computing applications on interconnection networks.

Trace Replay and Network Simulation Tool

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

Jain, Nikhil; Bhatele, Abhinav; Acun, Bilge

TraceR Is a trace replay tool built upon the ROSS-based CODES simulation framework. TraceR can be used for predicting network performance and understanding network behavior by simulating messaging In High Performance Computing applications on interconnection networks.

Trace-shortened Reed-Solomon codes

NASA Technical Reports Server (NTRS)

Mceliece, R. J.; Solomon, G.

1994-01-01

Reed-Solomon (RS) codes have been part of standard NASA telecommunications systems for many years. RS codes are character-oriented error-correcting codes, and their principal use in space applications has been as outer codes in concatenated coding systems. However, for a given character size, say m bits, RS codes are limited to a length of, at most, 2(exp m). It is known in theory that longer character-oriented codes would be superior to RS codes in concatenation applications, but until recently no practical class of 'long' character-oriented codes had been discovered. In 1992, however, Solomon discovered an extensive class of such codes, which are now called trace-shortened Reed-Solomon (TSRS) codes. In this article, we will continue the study of TSRS codes. Our main result is a formula for the dimension of any TSRS code, as a function of its error-correcting power. Using this formula, we will give several examples of TSRS codes, some of which look very promising as candidate outer codes in high-performance coded telecommunications systems.

Current Status of Post-combustor Trace Chemistry Modeling and Simulation at NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Wey, Thomas; Liu, Nan-Suey

2003-01-01

The overall objective of the current effort at NASA GRC is to evaluate, develop, and apply methodologies suitable for modeling intra-engine trace chemical changes over post combustor flow path relevant to the pollutant emissions from aircraft engines. At the present time, the focus is the high pressure turbine environment. At first, the trace chemistry model of CNEWT were implemented into GLENN-HT as well as NCC. Then, CNEWT, CGLENN-HT, and NCC were applied to the trace species evolution in a cascade of Cambridge University's No. 2 rotor and in a turbine vane passage. In general, the results from these different codes provide similar features. However, the details of some of the quantities of interest can be sensitive to the differences of these codes. This report summaries the implementation effort and presents the comparison of the No. 2 rotor results obtained from these different codes. The comparison of the turbine vane passage results is reported elsewhere. In addition to the implementation of trace chemistry model into existing CFD codes, several pre/post-processing tools that can handle the manipulations of the geometry, the unstructured and structured grids as well as the CFD solutions also have been enhanced and seamlessly tied with NCC, CGLENN-HT, and CNEWT. Thus, a complete CFD package consisting of pre/post-processing tools and flow solvers suitable for post-combustor intra-engine trace chemistry study is assembled.

A genetic scale of reading frame coding.

PubMed

Michel, Christian J

2014-08-21

The reading frame coding (RFC) of codes (sets) of trinucleotides is a genetic concept which has been largely ignored during the last 50 years. A first objective is the definition of a new and simple statistical parameter PrRFC for analysing the probability (efficiency) of reading frame coding (RFC) of any trinucleotide code. A second objective is to reveal different classes and subclasses of trinucleotide codes involved in reading frame coding: the circular codes of 20 trinucleotides and the bijective genetic codes of 20 trinucleotides coding the 20 amino acids. This approach allows us to propose a genetic scale of reading frame coding which ranges from 1/3 with the random codes (RFC probability identical in the three frames) to 1 with the comma-free circular codes (RFC probability maximal in the reading frame and null in the two shifted frames). This genetic scale shows, in particular, the reading frame coding probabilities of the 12,964,440 circular codes (PrRFC=83.2% in average), the 216 C(3) self-complementary circular codes (PrRFC=84.1% in average) including the code X identified in eukaryotic and prokaryotic genes (PrRFC=81.3%) and the 339,738,624 bijective genetic codes (PrRFC=61.5% in average) including the 52 codes without permuted trinucleotides (PrRFC=66.0% in average). Otherwise, the reading frame coding probabilities of each trinucleotide code coding an amino acid with the universal genetic code are also determined. The four amino acids Gly, Lys, Phe and Pro are coded by codes (not circular) with RFC probabilities equal to 2/3, 1/2, 1/2 and 2/3, respectively. The amino acid Leu is coded by a circular code (not comma-free) with a RFC probability equal to 18/19. The 15 other amino acids are coded by comma-free circular codes, i.e. with RFC probabilities equal to 1. The identification of coding properties in some classes of trinucleotide codes studied here may bring new insights in the origin and evolution of the genetic code. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genetic code, hamming distance and stochastic matrices.

PubMed

He, Matthew X; Petoukhov, Sergei V; Ricci, Paolo E

2004-09-01

In this paper we use the Gray code representation of the genetic code C=00, U=10, G=11 and A=01 (C pairs with G, A pairs with U) to generate a sequence of genetic code-based matrices. In connection with these code-based matrices, we use the Hamming distance to generate a sequence of numerical matrices. We then further investigate the properties of the numerical matrices and show that they are doubly stochastic and symmetric. We determine the frequency distributions of the Hamming distances, building blocks of the matrices, decomposition and iterations of matrices. We present an explicit decomposition formula for the genetic code-based matrix in terms of permutation matrices, which provides a hypercube representation of the genetic code. It is also observed that there is a Hamiltonian cycle in a genetic code-based hypercube.

Assessment of the TRACE Reactor Analysis Code Against Selected PANDA Transient Data

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

Zavisca, M.; Ghaderi, M.; Khatib-Rahbar, M.

2006-07-01

The TRACE (TRAC/RELAP Advanced Computational Engine) code is an advanced, best-estimate thermal-hydraulic program intended to simulate the transient behavior of light-water reactor systems, using a two-fluid (steam and water, with non-condensable gas), seven-equation representation of the conservation equations and flow-regime dependent constitutive relations in a component-based model with one-, two-, or three-dimensional elements, as well as solid heat structures and logical elements for the control system. The U.S. Nuclear Regulatory Commission is currently supporting the development of the TRACE code and its assessment against a variety of experimental data pertinent to existing and evolutionary reactor designs. This paper presents themore » results of TRACE post-test prediction of P-series of experiments (i.e., tests comprising the ISP-42 blind and open phases) conducted at the PANDA large-scale test facility in 1990's. These results show reasonable agreement with the reported test results, indicating good performance of the code and relevant underlying thermal-hydraulic and heat transfer models. (authors)« less

Two Perspectives on the Origin of the Standard Genetic Code

NASA Astrophysics Data System (ADS)

Sengupta, Supratim; Aggarwal, Neha; Bandhu, Ashutosh Vishwa

2014-12-01

The origin of a genetic code made it possible to create ordered sequences of amino acids. In this article we provide two perspectives on code origin by carrying out simulations of code-sequence coevolution in finite populations with the aim of examining how the standard genetic code may have evolved from more primitive code(s) encoding a small number of amino acids. We determine the efficacy of the physico-chemical hypothesis of code origin in the absence and presence of horizontal gene transfer (HGT) by allowing a diverse collection of code-sequence sets to compete with each other. We find that in the absence of horizontal gene transfer, natural selection between competing codes distinguished by differences in the degree of physico-chemical optimization is unable to explain the structure of the standard genetic code. However, for certain probabilities of the horizontal transfer events, a universal code emerges having a structure that is consistent with the standard genetic code.

A Measurement and Simulation Based Methodology for Cache Performance Modeling and Tuning

NASA Technical Reports Server (NTRS)

Waheed, Abdul; Yan, Jerry; Saini, Subhash (Technical Monitor)

1998-01-01

We present a cache performance modeling methodology that facilitates the tuning of uniprocessor cache performance for applications executing on shared memory multiprocessors by accurately predicting the effects of source code level modifications. Measurements on a single processor are initially used for identifying parts of code where cache utilization improvements may significantly impact the overall performance. Cache simulation based on trace-driven techniques can be carried out without gathering detailed address traces. Minimal runtime information for modeling cache performance of a selected code block includes: base virtual addresses of arrays, virtual addresses of variables, and loop bounds for that code block. Rest of the information is obtained from the source code. We show that the cache performance predictions are as reliable as those obtained through trace-driven simulations. This technique is particularly helpful to the exploration of various "what-if' scenarios regarding the cache performance impact for alternative code structures. We explain and validate this methodology using a simple matrix-matrix multiplication program. We then apply this methodology to predict and tune the cache performance of two realistic scientific applications taken from the Computational Fluid Dynamics (CFD) domain.

The aminoacyl-tRNA synthetases had only a marginal role in the origin of the organization of the genetic code: Evidence in favor of the coevolution theory.

PubMed

Di Giulio, Massimo

2017-11-07

The coevolution theory of the origin of the genetic code suggests that the organization of the genetic code coevolved with the biosynthetic relationships between amino acids. The mechanism that allowed this coevolution was based on tRNA-like molecules on which-this theory-would postulate the biosynthetic transformations between amino acids to have occurred. This mechanism makes a prediction on how the role conducted by the aminoacyl-tRNA synthetases (ARSs), in the origin of the genetic code, should have been. Indeed, if the biosynthetic transformations between amino acids occurred on tRNA-like molecules, then there was no need to link amino acids to these molecules because amino acids were already charged on tRNA-like molecules, as the coevolution theory suggests. In spite of the fact that ARSs make the genetic code responsible for the first interaction between a component of nucleic acids and that of proteins, for the coevolution theory the role of ARSs should have been entirely marginal in the genetic code origin. Therefore, I have conducted a further analysis of the distribution of the two classes of ARSs and of their subclasses-in the genetic code table-in order to perform a falsification test of the coevolution theory. Indeed, in the case in which the distribution of ARSs within the genetic code would have been highly significant, then the coevolution theory would be falsified since the mechanism on which it is based would not predict a fundamental role of ARSs in the origin of the genetic code. I found that the statistical significance of the distribution of the two classes of ARSs in the table of the genetic code is low or marginal, whereas that of the subclasses of ARSs statistically significant. However, this is in perfect agreement with the postulates of the coevolution theory. Indeed, the only case of statistical significance-regarding the classes of ARSs-is appreciable for the CAG code, whereas for its complement-the UNN/NUN code-only a marginal significance is measurable. These two codes codify roughly for the two ARS classes, in particular, the CAG code for the class II while the UNN/NUN code for the class I. Furthermore, the subclasses of ARSs show a statistical significance of their distribution in the genetic code table. Nevertheless, the more sensible explanation for these observations would be the following. The observation that would link the two classes of ARSs to the CAG and UNN/NUN codes, and the statistical significance of the distribution of the subclasses of ARSs in the genetic code table, would be only a secondary effect due to the highly significant distribution of the polarity of amino acids and their biosynthetic relationships in the genetic code. That is to say, the polarity of amino acids and their biosynthetic relationships would have conditioned the evolution of ARSs so that their presence in the genetic code would have been detectable. Even if the ARSs would not have-on their own-influenced directly the evolutionary organization of the genetic code. In other words, the role that ARSs had in the origin of the genetic code would have been entirely marginal. This conclusion would be in perfect accord with the predictions of the coevolution theory. Conversely, this conclusion would be in contrast-at least partially-with the physicochemical theories of the origin of the genetic code because they would foresee an absolutely more active role of ARSs in the origin of the organization of the genetic code. Copyright © 2017 Elsevier Ltd. All rights reserved.

Critical roles for a genetic code alteration in the evolution of the genus Candida.

PubMed

Silva, Raquel M; Paredes, João A; Moura, Gabriela R; Manadas, Bruno; Lima-Costa, Tatiana; Rocha, Rita; Miranda, Isabel; Gomes, Ana C; Koerkamp, Marian J G; Perrot, Michel; Holstege, Frank C P; Boucherie, Hélian; Santos, Manuel A S

2007-10-31

During the last 30 years, several alterations to the standard genetic code have been discovered in various bacterial and eukaryotic species. Sense and nonsense codons have been reassigned or reprogrammed to expand the genetic code to selenocysteine and pyrrolysine. These discoveries highlight unexpected flexibility in the genetic code, but do not elucidate how the organisms survived the proteome chaos generated by codon identity redefinition. In order to shed new light on this question, we have reconstructed a Candida genetic code alteration in Saccharomyces cerevisiae and used a combination of DNA microarrays, proteomics and genetics approaches to evaluate its impact on gene expression, adaptation and sexual reproduction. This genetic manipulation blocked mating, locked yeast in a diploid state, remodelled gene expression and created stress cross-protection that generated adaptive advantages under environmental challenging conditions. This study highlights unanticipated roles for codon identity redefinition during the evolution of the genus Candida, and strongly suggests that genetic code alterations create genetic barriers that speed up speciation.

A users' guide to the trace contaminant control simulation computer program

NASA Technical Reports Server (NTRS)

Perry, J. L.

1994-01-01

The Trace Contaminant Control Simulation computer program is a tool for assessing the performance of various trace contaminant control technologies for removing trace chemical contamination from a spacecraft cabin atmosphere. The results obtained from the program can be useful in assessing different technology combinations, system sizing, system location with respect to other life support systems, and the overall life cycle economics of a trace contaminant control system. The user's manual is extracted in its entirety from NASA TM-108409 to provide a stand-alone reference for using any version of the program. The first publication of the manual as part of TM-108409 also included a detailed listing of version 8.0 of the program. As changes to the code were necessary, it became apparent that the user's manual should be separate from the computer code documentation and be general enough to provide guidance in using any version of the program. Provided in the guide are tips for input file preparation, general program execution, and output file manipulation. Information concerning source code listings of the latest version of the computer program may be obtained by contacting the author.

Arbitrariness is not enough: towards a functional approach to the genetic code.

PubMed

Lacková, Ľudmila; Matlach, Vladimír; Faltýnek, Dan

2017-12-01

Arbitrariness in the genetic code is one of the main reasons for a linguistic approach to molecular biology: the genetic code is usually understood as an arbitrary relation between amino acids and nucleobases. However, from a semiotic point of view, arbitrariness should not be the only condition for definition of a code, consequently it is not completely correct to talk about "code" in this case. Yet we suppose that there exist a code in the process of protein synthesis, but on a higher level than the nucleic bases chains. Semiotically, a code should be always associated with a function and we propose to define the genetic code not only relationally (in basis of relation between nucleobases and amino acids) but also in terms of function (function of a protein as meaning of the code). Even if the functional definition of meaning in the genetic code has been discussed in the field of biosemiotics, its further implications have not been considered. In fact, if the function of a protein represents the meaning of the genetic code (the sign's object), then it is crucial to reconsider the notion of its expression (the sign) as well. In our contribution, we will show that the actual model of the genetic code is not the only possible and we will propose a more appropriate model from a semiotic point of view.

Mise en Scene: Conversion of Scenarios to CSP Traces for the Requirements-to-Design-to-Code Project

NASA Technical Reports Server (NTRS)

Carter. John D.; Gardner, William B.; Rash, James L.; Hinchey, Michael G.

2007-01-01

The "Requirements-to-Design-to-Code" (R2D2C) project at NASA's Goddard Space Flight Center is based on deriving a formal specification expressed in Communicating Sequential Processes (CSP) notation from system requirements supplied in the form of CSP traces. The traces, in turn, are to be extracted from scenarios, a user-friendly medium often used to describe the required behavior of computer systems under development. This work, called Mise en Scene, defines a new scenario medium (Scenario Notation Language, SNL) suitable for control-dominated systems, coupled with a two-stage process for automatic translation of scenarios to a new trace medium (Trace Notation Language, TNL) that encompasses CSP traces. Mise en Scene is offered as an initial solution to the problem of the scenarios-to-traces "D2" phase of R2D2C. A survey of the "scenario" concept and some case studies are also provided.

Alignment-based and alignment-free methods converge with experimental data on amino acids coded by stop codons at split between nuclear and mitochondrial genetic codes.

PubMed

Seligmann, Hervé

2018-05-01

Genetic codes mainly evolve by reassigning punctuation codons, starts and stops. Previous analyses assuming that undefined amino acids translate stops showed greater divergence between nuclear and mitochondrial genetic codes. Here, three independent methods converge on which amino acids translated stops at split between nuclear and mitochondrial genetic codes: (a) alignment-free genetic code comparisons inserting different amino acids at stops; (b) alignment-based blast analyses of hypothetical peptides translated from non-coding mitochondrial sequences, inserting different amino acids at stops; (c) biases in amino acid insertions at stops in proteomic data. Hence short-term protein evolution models reconstruct long-term genetic code evolution. Mitochondria reassign stops to amino acids otherwise inserted at stops by codon-anticodon mismatches (near-cognate tRNAs). Hence dual function (translation termination and translation by codon-anticodon mismatch) precedes mitochondrial reassignments of stops to amino acids. Stop ambiguity increases coded information, compensates endocellular mitogenome reduction. Mitochondrial codon reassignments might prevent viral infections. Copyright © 2018 Elsevier B.V. All rights reserved.

A specific indel marker for the Philippines Schistosoma japonicum revealed by analysis of mitochondrial genome sequences.

PubMed

Li, Juan; Chen, Fen; Sugiyama, Hiromu; Blair, David; Lin, Rui-Qing; Zhu, Xing-Quan

2015-07-01

In the present study, near-complete mitochondrial (mt) genome sequences for Schistosoma japonicum from different regions in the Philippines and Japan were amplified and sequenced. Comparisons among S. japonicum from the Philippines, Japan, and China revealed a geographically based length difference in mt genomes, but the mt genomic organization and gene arrangement were the same. Sequence differences among samples from the Philippines and all samples from the three endemic areas were 0.57-2.12 and 0.76-3.85 %, respectively. The most variable part of the mt genome was the non-coding region. In the coding portion of the genome, protein-coding genes varied more than rRNA genes and tRNAs. The near-complete mt genome sequences for Philippine specimens were identical in length (14,091 bp) which was 4 bp longer than those of S. japonicum samples from Japan and China. This indel provides a unique genetic marker for S. japonicum samples from the Philippines. Phylogenetic analyses based on the concatenated amino acids of 12 protein-coding genes showed that samples of S. japonicum clustered according to their geographical origins. The identified mitochondrial indel marker will be useful for tracing the source of S. japonicum infection in humans and animals in Southeast Asia.

Should I Perform Genetic Testing? A Qualitative Look into the Decision Making Considerations of Religious Israeli Undergraduate Students.

PubMed

Siani, Merav; Assaraf, Orit Ben-Zvi

2016-10-01

The aim of this study is to draw a picture of the concerns that guide the decision making of Israeli religious undergraduate students and the complex considerations they take into account while facing the need to have genetic testing or to attend a genetic counseling session. We examined how the religious affiliation of the students influences their perceptions toward genetics and how these are expressed. Qualitative data were collected from 51 semi-structured interviews with students, in which recurring themes were identified using 'thematic analysis.' The codes from the thematic analysis were obtained according to 'grounded theory'. Our results show that religious undergraduate students' decision making in these issues is influenced by factors that fall under three main categories: knowledge and perceptions, values, and norms. In order to include all the components of influence, we created the Triple C model: "Culture influences Choices towards genetic Counseling" which aims to generalize the complex decision making considerations that we detected. Our model places religion, as part of culture, as its central point of influence that impacts all three of the main categories we detected. It also traces the bidirectional influences that each of these main categories have on one another. Using this model may help identify the sociocultural differences between different types of patients, helping genetic counselors to better assist them in addressing their genetic status by tailoring the counseling more specifically to the patient's cultural uniqueness.

Solar Proton Transport Within an ICRU Sphere Surrounded by a Complex Shield: Ray-trace Geometry

NASA Technical Reports Server (NTRS)

Slaba, Tony C.; Wilson, John W.; Badavi, Francis F.; Reddell, Brandon D.; Bahadori, Amir A.

2015-01-01

A computationally efficient 3DHZETRN code with enhanced neutron and light ion (Z is less than or equal to 2) propagation was recently developed for complex, inhomogeneous shield geometry described by combinatorial objects. Comparisons were made between 3DHZETRN results and Monte Carlo (MC) simulations at locations within the combinatorial geometry, and it was shown that 3DHZETRN agrees with the MC codes to the extent they agree with each other. In the present report, the 3DHZETRN code is extended to enable analysis in ray-trace geometry. This latest extension enables the code to be used within current engineering design practices utilizing fully detailed vehicle and habitat geometries. Through convergence testing, it is shown that fidelity in an actual shield geometry can be maintained in the discrete ray-trace description by systematically increasing the number of discrete rays used. It is also shown that this fidelity is carried into transport procedures and resulting exposure quantities without sacrificing computational efficiency.

Solar proton exposure of an ICRU sphere within a complex structure part II: Ray-trace geometry.

PubMed

Slaba, Tony C; Wilson, John W; Badavi, Francis F; Reddell, Brandon D; Bahadori, Amir A

2016-06-01

A computationally efficient 3DHZETRN code with enhanced neutron and light ion (Z ≤ 2) propagation was recently developed for complex, inhomogeneous shield geometry described by combinatorial objects. Comparisons were made between 3DHZETRN results and Monte Carlo (MC) simulations at locations within the combinatorial geometry, and it was shown that 3DHZETRN agrees with the MC codes to the extent they agree with each other. In the present report, the 3DHZETRN code is extended to enable analysis in ray-trace geometry. This latest extension enables the code to be used within current engineering design practices utilizing fully detailed vehicle and habitat geometries. Through convergence testing, it is shown that fidelity in an actual shield geometry can be maintained in the discrete ray-trace description by systematically increasing the number of discrete rays used. It is also shown that this fidelity is carried into transport procedures and resulting exposure quantities without sacrificing computational efficiency. Published by Elsevier Ltd.

Genetic Code Analysis Toolkit: A novel tool to explore the coding properties of the genetic code and DNA sequences

NASA Astrophysics Data System (ADS)

Kraljić, K.; Strüngmann, L.; Fimmel, E.; Gumbel, M.

2018-01-01

The genetic code is degenerated and it is assumed that redundancy provides error detection and correction mechanisms in the translation process. However, the biological meaning of the code's structure is still under current research. This paper presents a Genetic Code Analysis Toolkit (GCAT) which provides workflows and algorithms for the analysis of the structure of nucleotide sequences. In particular, sets or sequences of codons can be transformed and tested for circularity, comma-freeness, dichotomic partitions and others. GCAT comes with a fertile editor custom-built to work with the genetic code and a batch mode for multi-sequence processing. With the ability to read FASTA files or load sequences from GenBank, the tool can be used for the mathematical and statistical analysis of existing sequence data. GCAT is Java-based and provides a plug-in concept for extensibility. Availability: Open source Homepage:http://www.gcat.bio/

Mapping and Deciphering Neural Codes of NMDA Receptor-Dependent Fear Memory Engrams in the Hippocampus

PubMed Central

Tsien, Joe Z.

2013-01-01

Mapping and decoding brain activity patterns underlying learning and memory represents both great interest and immense challenge. At present, very little is known regarding many of the very basic questions regarding the neural codes of memory: are fear memories retrieved during the freezing state or non-freezing state of the animals? How do individual memory traces give arise to a holistic, real-time associative memory engram? How are memory codes regulated by synaptic plasticity? Here, by applying high-density electrode arrays and dimensionality-reduction decoding algorithms, we investigate hippocampal CA1 activity patterns of trace fear conditioning memory code in inducible NMDA receptor knockout mice and their control littermates. Our analyses showed that the conditioned tone (CS) and unconditioned foot-shock (US) can evoke hippocampal ensemble responses in control and mutant mice. Yet, temporal formats and contents of CA1 fear memory engrams differ significantly between the genotypes. The mutant mice with disabled NMDA receptor plasticity failed to generate CS-to-US or US-to-CS associative memory traces. Moreover, the mutant CA1 region lacked memory traces for “what at when” information that predicts the timing relationship between the conditioned tone and the foot shock. The degraded associative fear memory engram is further manifested in its lack of intertwined and alternating temporal association between CS and US memory traces that are characteristic to the holistic memory recall in the wild-type animals. Therefore, our study has decoded real-time memory contents, timing relationship between CS and US, and temporal organizing patterns of fear memory engrams and demonstrated how hippocampal memory codes are regulated by NMDA receptor synaptic plasticity. PMID:24302990

Trace amine-associated receptors and their ligands

PubMed Central

Zucchi, R; Chiellini, G; Scanlan, T S; Grandy, D K

2006-01-01

Classical biogenic amines (adrenaline, noradrenaline, dopamine, serotonin and histamine) interact with specific families of G protein-coupled receptors (GPCRs). The term ‘trace amines' is used when referring to p-tyramine, β-phenylethylamine, tryptamine and octopamine, compounds that are present in mammalian tissues at very low (nanomolar) concentrations. The pharmacological effects of trace amines are usually attributed to their interference with the aminergic pathways, but in 2001 a new gene was identified, that codes for a GPCR responding to p-tyramine and β-phenylethylamine but not to classical biogenic amines. Several closely related genes were subsequently identified and designated as the trace amine-associated receptors (TAARs). Pharmacological investigations in vitro show that many TAAR subtypes may not respond to p-tyramine, β-phenylethylamine, tryptamine or octopamine, suggesting the existence of additional endogenous ligands. A novel endogenous thyroid hormone derivative, 3-iodothyronamine, has been found to interact with TAAR1 and possibly other TAAR subtypes. In vivo, micromolar concentrations of 3-iodothyronamine determine functional effects which are opposite to those produced on a longer time scale by thyroid hormones, including reduction in body temperature and decrease in cardiac contractility. Expression of all TAAR subtypes except TAAR1 has been reported in mouse olfactory epithelium, and several volatile amines were shown to interact with specific TAAR subtypes. In addition, there is evidence that TAAR1 is targeted by amphetamines and other psychotropic agents, while genetic linkage studies show a significant association between the TAAR gene family locus and susceptibility to schizophrenia or bipolar affective disorder. PMID:17088868

Mechanistic Insights Into Catalytic RNA-Protein Complexes Involved in Translation of the Genetic Code.

PubMed

Routh, Satya B; Sankaranarayanan, Rajan

2017-01-01

The contemporary world is an "RNA-protein world" rather than a "protein world" and tracing its evolutionary origins is of great interest and importance. The different RNAs that function in close collaboration with proteins are involved in several key physiological processes, including catalysis. Ribosome-the complex megadalton cellular machinery that translates genetic information encoded in nucleotide sequence to amino acid sequence-epitomizes such an association between RNA and protein. RNAs that can catalyze biochemical reactions are known as ribozymes. They usually employ general acid-base catalytic mechanism, often involving the 2'-OH of RNA that activates and/or stabilizes a nucleophile during the reaction pathway. The protein component of such RNA-protein complexes (RNPCs) mostly serves as a scaffold which provides an environment conducive for the RNA to function, or as a mediator for other interacting partners. In this review, we describe those RNPCs that are involved at different stages of protein biosynthesis and in which RNA performs the catalytic function; the focus of the account is on highlighting mechanistic aspects of these complexes. We also provide a perspective on such associations in the context of proofreading during translation of the genetic code. The latter aspect is not much appreciated and recent works suggest that this is an avenue worth exploring, since an understanding of the subject can provide useful insights into how RNAs collaborate with proteins to ensure fidelity during these essential cellular processes. It may also aid in comprehending evolutionary aspects of such associations. © 2017 Elsevier Inc. All rights reserved.

An analysis of options available for developing a common laser ray tracing package for Ares and Kull code frameworks

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

Weeratunga, S K

Ares and Kull are mature code frameworks that support ALE hydrodynamics for a variety of HEDP applications at LLNL, using two widely different meshing approaches. While Ares is based on a 2-D/3-D block-structured mesh data base, Kull is designed to support unstructured, arbitrary polygonal/polyhedral meshes. In addition, both frameworks are capable of running applications on large, distributed-memory parallel machines. Currently, both these frameworks separately support assorted collections of physics packages related to HEDP, including one for the energy deposition by laser/ion-beam ray tracing. This study analyzes the options available for developing a common laser/ion-beam ray tracing package that can bemore » easily shared between these two code frameworks and concludes with a set of recommendations for its development.« less

Mathematical fundamentals for the noise immunity of the genetic code.

PubMed

Fimmel, Elena; Strüngmann, Lutz

2018-02-01

Symmetry is one of the essential and most visible patterns that can be seen in nature. Starting from the left-right symmetry of the human body, all types of symmetry can be found in crystals, plants, animals and nature as a whole. Similarly, principals of symmetry are also some of the fundamental and most useful tools in modern mathematical natural science that play a major role in theory and applications. As a consequence, it is not surprising that the desire to understand the origin of life, based on the genetic code, forces us to involve symmetry as a mathematical concept. The genetic code can be seen as a key to biological self-organisation. All living organisms have the same molecular bases - an alphabet consisting of four letters (nitrogenous bases): adenine, cytosine, guanine, and thymine. Linearly ordered sequences of these bases contain the genetic information for synthesis of proteins in all forms of life. Thus, one of the most fascinating riddles of nature is to explain why the genetic code is as it is. Genetic coding possesses noise immunity which is the fundamental feature that allows to pass on the genetic information from parents to their descendants. Hence, since the time of the discovery of the genetic code, scientists have tried to explain the noise immunity of the genetic information. In this chapter we will discuss recent results in mathematical modelling of the genetic code with respect to noise immunity, in particular error-detection and error-correction. We will focus on two central properties: Degeneracy and frameshift correction. Different amino acids are encoded by different quantities of codons and a connection between this degeneracy and the noise immunity of genetic information is a long standing hypothesis. Biological implications of the degeneracy have been intensively studied and whether the natural code is a frozen accident or a highly optimised product of evolution is still controversially discussed. Symmetries in the structure of degeneracy of the genetic code are essential and give evidence of substantial advantages of the natural code over other possible ones. In the present chapter we will present a recent approach to explain the degeneracy of the genetic code by algorithmic methods from bioinformatics, and discuss its biological consequences. The biologists recognised this problem immediately after the detection of the non-overlapping structure of the genetic code, i.e., coding sequences are to be read in a unique way determined by their reading frame. But how does the reading head of the ribosome recognises an error in the grouping of codons, caused by e.g. insertion or deletion of a base, that can be fatal during the translation process and may result in nonfunctional proteins? In this chapter we will discuss possible solutions to the frameshift problem with a focus on the theory of so-called circular codes that were discovered in large gene populations of prokaryotes and eukaryotes in the early 90s. Circular codes allow to detect a frameshift of one or two positions and recently a beautiful theory of such codes has been developed using statistics, group theory and graph theory. Copyright © 2017 Elsevier B.V. All rights reserved.

The neutral emergence of error minimized genetic codes superior to the standard genetic code.

PubMed

Massey, Steven E

2016-11-07

The standard genetic code (SGC) assigns amino acids to codons in such a way that the impact of point mutations is reduced, this is termed 'error minimization' (EM). The occurrence of EM has been attributed to the direct action of selection, however it is difficult to explain how the searching of alternative codes for an error minimized code can occur via codon reassignments, given that these are likely to be disruptive to the proteome. An alternative scenario is that EM has arisen via the process of genetic code expansion, facilitated by the duplication of genes encoding charging enzymes and adaptor molecules. This is likely to have led to similar amino acids being assigned to similar codons. Strikingly, we show that if during code expansion the most similar amino acid to the parent amino acid, out of the set of unassigned amino acids, is assigned to codons related to those of the parent amino acid, then genetic codes with EM superior to the SGC easily arise. This scheme mimics code expansion via the gene duplication of charging enzymes and adaptors. The result is obtained for a variety of different schemes of genetic code expansion and provides a mechanistically realistic manner in which EM has arisen in the SGC. These observations might be taken as evidence for self-organization in the earliest stages of life. Copyright © 2016 Elsevier Ltd. All rights reserved.

Environmental Ethics and Civil Engineering.

ERIC Educational Resources Information Center

Vesilind, P. Aarne

1987-01-01

Traces the development of the civil engineering code of ethics. Points out that the code does have an enforceable provision that addresses the engineer's responsibility toward the environment. Suggests revisions to the code to accommodate the environmental impacts of civil engineering. (TW)

SolTrace Background | Concentrating Solar Power | NREL

Science.gov Websites

codes was written to model a very specific optical geometry, and each one built upon the others in an evolutionary way. Examples of such codes include: OPTDSH, a code written to model circular aperture parabolic

Coevolution Theory of the Genetic Code at Age Forty: Pathway to Translation and Synthetic Life

PubMed Central

Wong, J. Tze-Fei; Ng, Siu-Kin; Mat, Wai-Kin; Hu, Taobo; Xue, Hong

2016-01-01

The origins of the components of genetic coding are examined in the present study. Genetic information arose from replicator induction by metabolite in accordance with the metabolic expansion law. Messenger RNA and transfer RNA stemmed from a template for binding the aminoacyl-RNA synthetase ribozymes employed to synthesize peptide prosthetic groups on RNAs in the Peptidated RNA World. Coevolution of the genetic code with amino acid biosynthesis generated tRNA paralogs that identify a last universal common ancestor (LUCA) of extant life close to Methanopyrus, which in turn points to archaeal tRNA introns as the most primitive introns and the anticodon usage of Methanopyrus as an ancient mode of wobble. The prediction of the coevolution theory of the genetic code that the code should be a mutable code has led to the isolation of optional and mandatory synthetic life forms with altered protein alphabets. PMID:26999216

Modelling Metamorphism by Abstract Interpretation

NASA Astrophysics Data System (ADS)

Dalla Preda, Mila; Giacobazzi, Roberto; Debray, Saumya; Coogan, Kevin; Townsend, Gregg M.

Metamorphic malware apply semantics-preserving transformations to their own code in order to foil detection systems based on signature matching. In this paper we consider the problem of automatically extract metamorphic signatures from these malware. We introduce a semantics for self-modifying code, later called phase semantics, and prove its correctness by showing that it is an abstract interpretation of the standard trace semantics. Phase semantics precisely models the metamorphic code behavior by providing a set of traces of programs which correspond to the possible evolutions of the metamorphic code during execution. We show that metamorphic signatures can be automatically extracted by abstract interpretation of the phase semantics, and that regular metamorphism can be modelled as finite state automata abstraction of the phase semantics.

Crucial steps to life: From chemical reactions to code using agents.

PubMed

Witzany, Guenther

2016-02-01

The concepts of the origin of the genetic code and the definitions of life changed dramatically after the RNA world hypothesis. Main narratives in molecular biology and genetics such as the "central dogma," "one gene one protein" and "non-coding DNA is junk" were falsified meanwhile. RNA moved from the transition intermediate molecule into centre stage. Additionally the abundance of empirical data concerning non-random genetic change operators such as the variety of mobile genetic elements, persistent viruses and defectives do not fit with the dominant narrative of error replication events (mutations) as being the main driving forces creating genetic novelty and diversity. The reductionistic and mechanistic views on physico-chemical properties of the genetic code are no longer convincing as appropriate descriptions of the abundance of non-random genetic content operators which are active in natural genetic engineering and natural genome editing. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

Epiney, A.; Canepa, S.; Zerkak, O.

The STARS project at the Paul Scherrer Institut (PSI) has adopted the TRACE thermal-hydraulic (T-H) code for best-estimate system transient simulations of the Swiss Light Water Reactors (LWRs). For analyses involving interactions between system and core, a coupling of TRACE with the SIMULATE-3K (S3K) LWR core simulator has also been developed. In this configuration, the TRACE code and associated nuclear power reactor simulation models play a central role to achieve a comprehensive safety analysis capability. Thus, efforts have now been undertaken to consolidate the validation strategy by implementing a more rigorous and structured assessment approach for TRACE applications involving eithermore » only system T-H evaluations or requiring interfaces to e.g. detailed core or fuel behavior models. The first part of this paper presents the preliminary concepts of this validation strategy. The principle is to systematically track the evolution of a given set of predicted physical Quantities of Interest (QoIs) over a multidimensional parametric space where each of the dimensions represent the evolution of specific analysis aspects, including e.g. code version, transient specific simulation methodology and model "nodalisation". If properly set up, such environment should provide code developers and code users with persistent (less affected by user effect) and quantified information (sensitivity of QoIs) on the applicability of a simulation scheme (codes, input models, methodology) for steady state and transient analysis of full LWR systems. Through this, for each given transient/accident, critical paths of the validation process can be identified that could then translate into defining reference schemes to be applied for downstream predictive simulations. In order to illustrate this approach, the second part of this paper presents a first application of this validation strategy to an inadvertent blowdown event that occurred in a Swiss BWR/6. The transient was initiated by the spurious actuation of the Automatic Depressurization System (ADS). The validation approach progresses through a number of dimensions here: First, the same BWR system simulation model is assessed for different versions of the TRACE code, up to the most recent one. The second dimension is the "nodalisation" dimension, where changes to the input model are assessed. The third dimension is the "methodology" dimension. In this case imposed power and an updated TRACE core model are investigated. For each step in each validation dimension, a common set of QoIs are investigated. For the steady-state results, these include fuel temperatures distributions. For the transient part of the present study, the evaluated QoIs include the system pressure evolution and water carry-over into the steam line.« less

Contribution of finger tracing to the recognition of Chinese characters.

PubMed

Yim-Ng, Y Y; Varley, R; Andrade, J

2000-01-01

Finger tracing is a simulation of the act of writing without the use of pen and paper. It is claimed to help in the processing of Chinese characters, possibly by providing additional motor coding. In this study, blindfolded subjects were equally good at identifying Chinese characters and novel visual stimuli through passive movements made with the index finger of the preferred hand and those made with the last finger of that hand. This suggests that finger tracing provides a relatively high level of coding specific to individual characters, but non-specific to motor effectors. Beginning each stroke from the same location, i.e. removing spatial information, impaired recognition of the familiar characters and the novel nonsense figures. Passively tracing the strokes in a random sequence also impaired recognition of the characters. These results therefore suggest that the beneficial effect of finger tracing on writing or recall of Chinese characters is mediated by sequence and spatial information embedded in the motor movements, and that proprioceptive channel may play a part in mediating visuo-spatial information. Finger tracing may be a useful strategy for remediation of Chinese language impairments.

A discriminative test among the different theories proposed to explain the origin of the genetic code: the coevolution theory finds additional support.

PubMed

Giulio, Massimo Di

2018-05-19

A discriminative statistical test among the different theories proposed to explain the origin of the genetic code is presented. Gathering the amino acids into polarity and biosynthetic classes that are the first expression of the physicochemical theory of the origin of the genetic code and the second expression of the coevolution theory, these classes are utilized in the Fisher's exact test to establish their significance within the genetic code table. Linking to the rows and columns of the genetic code of probabilities that express the statistical significance of these classes, I have finally been in the condition to be able to calculate a χ value to link to both the physicochemical theory and to the coevolution theory that would express the corroboration level referred to these theories. The comparison between these two χ values showed that the coevolution theory is able to explain - in this strictly empirical analysis - the origin of the genetic code better than that of the physicochemical theory. Copyright © 2018 Elsevier B.V. All rights reserved.

Digitized forensics: retaining a link between physical and digital crime scene traces using QR-codes

NASA Astrophysics Data System (ADS)

Hildebrandt, Mario; Kiltz, Stefan; Dittmann, Jana

2013-03-01

The digitization of physical traces from crime scenes in forensic investigations in effect creates a digital chain-of-custody and entrains the challenge of creating a link between the two or more representations of the same trace. In order to be forensically sound, especially the two security aspects of integrity and authenticity need to be maintained at all times. Especially the adherence to the authenticity using technical means proves to be a challenge at the boundary between the physical object and its digital representations. In this article we propose a new method of linking physical objects with its digital counterparts using two-dimensional bar codes and additional meta-data accompanying the acquired data for integration in the conventional documentation of collection of items of evidence (bagging and tagging process). Using the exemplary chosen QR-code as particular implementation of a bar code and a model of the forensic process, we also supply a means to integrate our suggested approach into forensically sound proceedings as described by Holder et al.1 We use the example of the digital dactyloscopy as a forensic discipline, where currently progress is being made by digitizing some of the processing steps. We show an exemplary demonstrator of the suggested approach using a smartphone as a mobile device for the verification of the physical trace to extend the chain-of-custody from the physical to the digital domain. Our evaluation of the demonstrator is performed towards the readability and the verification of its contents. We can read the bar code despite its limited size of 42 x 42 mm and rather large amount of embedded data using various devices. Furthermore, the QR-code's error correction features help to recover contents of damaged codes. Subsequently, our appended digital signature allows for detecting malicious manipulations of the embedded data.

Inclusion of the fitness sharing technique in an evolutionary algorithm to analyze the fitness landscape of the genetic code adaptability.

PubMed

Santos, José; Monteagudo, Ángel

2017-03-27

The canonical code, although prevailing in complex genomes, is not universal. It was shown the canonical genetic code superior robustness compared to random codes, but it is not clearly determined how it evolved towards its current form. The error minimization theory considers the minimization of point mutation adverse effect as the main selection factor in the evolution of the code. We have used simulated evolution in a computer to search for optimized codes, which helps to obtain information about the optimization level of the canonical code in its evolution. A genetic algorithm searches for efficient codes in a fitness landscape that corresponds with the adaptability of possible hypothetical genetic codes. The lower the effects of errors or mutations in the codon bases of a hypothetical code, the more efficient or optimal is that code. The inclusion of the fitness sharing technique in the evolutionary algorithm allows the extent to which the canonical genetic code is in an area corresponding to a deep local minimum to be easily determined, even in the high dimensional spaces considered. The analyses show that the canonical code is not in a deep local minimum and that the fitness landscape is not a multimodal fitness landscape with deep and separated peaks. Moreover, the canonical code is clearly far away from the areas of higher fitness in the landscape. Given the non-presence of deep local minima in the landscape, although the code could evolve and different forces could shape its structure, the fitness landscape nature considered in the error minimization theory does not explain why the canonical code ended its evolution in a location which is not an area of a localized deep minimum of the huge fitness landscape.

A Bayesian network coding scheme for annotating biomedical information presented to genetic counseling clients.

PubMed

Green, Nancy

2005-04-01

We developed a Bayesian network coding scheme for annotating biomedical content in layperson-oriented clinical genetics documents. The coding scheme supports the representation of probabilistic and causal relationships among concepts in this domain, at a high enough level of abstraction to capture commonalities among genetic processes and their relationship to health. We are using the coding scheme to annotate a corpus of genetic counseling patient letters as part of the requirements analysis and knowledge acquisition phase of a natural language generation project. This paper describes the coding scheme and presents an evaluation of intercoder reliability for its tag set. In addition to giving examples of use of the coding scheme for analysis of discourse and linguistic features in this genre, we suggest other uses for it in analysis of layperson-oriented text and dialogue in medical communication.

An algebraic hypothesis about the primeval genetic code architecture.

PubMed

Sánchez, Robersy; Grau, Ricardo

2009-09-01

A plausible architecture of an ancient genetic code is derived from an extended base triplet vector space over the Galois field of the extended base alphabet {D,A,C,G,U}, where symbol D represents one or more hypothetical bases with unspecific pairings. We hypothesized that the high degeneration of a primeval genetic code with five bases and the gradual origin and improvement of a primeval DNA repair system could make possible the transition from ancient to modern genetic codes. Our results suggest that the Watson-Crick base pairing G identical with C and A=U and the non-specific base pairing of the hypothetical ancestral base D used to define the sum and product operations are enough features to determine the coding constraints of the primeval and the modern genetic code, as well as, the transition from the former to the latter. Geometrical and algebraic properties of this vector space reveal that the present codon assignment of the standard genetic code could be induced from a primeval codon assignment. Besides, the Fourier spectrum of the extended DNA genome sequences derived from the multiple sequence alignment suggests that the called period-3 property of the present coding DNA sequences could also exist in the ancient coding DNA sequences. The phylogenetic analyses achieved with metrics defined in the N-dimensional vector space (B(3))(N) of DNA sequences and with the new evolutionary model presented here also suggest that an ancient DNA coding sequence with five or more bases does not contradict the expected evolutionary history.

Analysis of the Effect of Electron Density Perturbations Generated by Gravity Waves on HF Communication Links

NASA Astrophysics Data System (ADS)

Fagre, M.; Elias, A. G.; Chum, J.; Cabrera, M. A.

2017-12-01

In the present work, ray tracing of high frequency (HF) signals in ionospheric disturbed conditions is analyzed, particularly in the presence of electron density perturbations generated by gravity waves (GWs). The three-dimensional numerical ray tracing code by Jones and Stephenson, based on Hamilton's equations, which is commonly used to study radio propagation through the ionosphere, is used. An electron density perturbation model is implemented to this code based upon the consideration of atmospheric GWs generated at a height of 150 km in the thermosphere and propagating up into the ionosphere. The motion of the neutral gas at these altitudes induces disturbances in the background plasma which affects HF signals propagation. To obtain a realistic model of GWs in order to analyze the propagation and dispersion characteristics, a GW ray tracing method with kinematic viscosity and thermal diffusivity was applied. The IRI-2012, HWM14 and NRLMSISE-00 models were incorporated to assess electron density, wind velocities, neutral temperature and total mass density needed for the ray tracing codes. Preliminary results of gravity wave effects on ground range and reflection height are presented for low-mid latitude ionosphere.

Review Of Piping And Pressure Vessel Code Design Criteria. Technical Report 217.

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

None, None

1969-04-18

This Technical Report summarizes a review of the design philosophies and criteria of the ASME Boiler and Pressure Vessel Code and the USASI Code for Pressure Piping. It traces the history of the Codes since their inception and critically reviews their present status. Recommendations are made concerning the applicability of the Codes to the special needs of LMFBR liquid sodium piping.

Reassigning stop codons via translation termination: How a few eukaryotes broke the dogma.

PubMed

Alkalaeva, Elena; Mikhailova, Tatiana

2017-03-01

The genetic code determines how amino acids are encoded within mRNA. It is universal among the vast majority of organisms, although several exceptions are known. Variant genetic codes are found in ciliates, mitochondria, and numerous other organisms. All revealed genetic codes (standard and variant) have at least one codon encoding a translation stop signal. However, recently two new genetic codes with a reassignment of all three stop codons were revealed in studies examining the protozoa transcriptomes. Here, we discuss this finding and the recent studies of variant genetic codes in eukaryotes. We consider the possible molecular mechanisms allowing the use of certain codons as sense and stop signals simultaneously. The results obtained by studying these amazing organisms represent a new and exciting insight into the mechanism of stop codon decoding in eukaryotes. Also see the video abstract here. © 2017 WILEY Periodicals, Inc.

Genetic hotels for the standard genetic code: evolutionary analysis based upon novel three-dimensional algebraic models.

PubMed

José, Marco V; Morgado, Eberto R; Govezensky, Tzipe

2011-07-01

Herein, we rigorously develop novel 3-dimensional algebraic models called Genetic Hotels of the Standard Genetic Code (SGC). We start by considering the primeval RNA genetic code which consists of the 16 codons of type RNY (purine-any base-pyrimidine). Using simple algebraic operations, we show how the RNA code could have evolved toward the current SGC via two different intermediate evolutionary stages called Extended RNA code type I and II. By rotations or translations of the subset RNY, we arrive at the SGC via the former (type I) or via the latter (type II), respectively. Biologically, the Extended RNA code type I, consists of all codons of the type RNY plus codons obtained by considering the RNA code but in the second (NYR type) and third (YRN type) reading frames. The Extended RNA code type II, comprises all codons of the type RNY plus codons that arise from transversions of the RNA code in the first (YNY type) and third (RNR) nucleotide bases. Since the dimensions of remarkable subsets of the Genetic Hotels are not necessarily integer numbers, we also introduce the concept of algebraic fractal dimension. A general decoding function which maps each codon to its corresponding amino acid or the stop signals is also derived. The Phenotypic Hotel of amino acids is also illustrated. The proposed evolutionary paths are discussed in terms of the existing theories of the evolution of the SGC. The adoption of 3-dimensional models of the Genetic and Phenotypic Hotels will facilitate the understanding of the biological properties of the SGC.

Structural Phylogenomics Retrodicts the Origin of the Genetic Code and Uncovers the Evolutionary Impact of Protein Flexibility

PubMed Central

Caetano-Anollés, Gustavo; Wang, Minglei; Caetano-Anollés, Derek

2013-01-01

The genetic code shapes the genetic repository. Its origin has puzzled molecular scientists for over half a century and remains a long-standing mystery. Here we show that the origin of the genetic code is tightly coupled to the history of aminoacyl-tRNA synthetase enzymes and their interactions with tRNA. A timeline of evolutionary appearance of protein domain families derived from a structural census in hundreds of genomes reveals the early emergence of the ‘operational’ RNA code and the late implementation of the standard genetic code. The emergence of codon specificities and amino acid charging involved tight coevolution of aminoacyl-tRNA synthetases and tRNA structures as well as episodes of structural recruitment. Remarkably, amino acid and dipeptide compositions of single-domain proteins appearing before the standard code suggest archaic synthetases with structures homologous to catalytic domains of tyrosyl-tRNA and seryl-tRNA synthetases were capable of peptide bond formation and aminoacylation. Results reveal that genetics arose through coevolutionary interactions between polypeptides and nucleic acid cofactors as an exacting mechanism that favored flexibility and folding of the emergent proteins. These enhancements of phenotypic robustness were likely internalized into the emerging genetic system with the early rise of modern protein structure. PMID:23991065

Genetic lineage tracing identifies in situ Kit-expressing cardiomyocytes

PubMed Central

Liu, Qiaozhen; Yang, Rui; Huang, Xiuzhen; Zhang, Hui; He, Lingjuan; Zhang, Libo; Tian, Xueying; Nie, Yu; Hu, Shengshou; Yan, Yan; Zhang, Li; Qiao, Zengyong; Wang, Qing-Dong; Lui, Kathy O; Zhou, Bin

2016-01-01

Cardiac cells marked by c-Kit or Kit, dubbed cardiac stem cells (CSCs), are in clinical trials to investigate their ability to stimulate cardiac regeneration and repair. These studies were initially motivated by the purported cardiogenic activity of these cells. Recent lineage tracing studies using Kit promoter to drive expression of the inducible Cre recombinase showed that these CSCs had highly limited cardiogenic activity, inadequate to support efficient cardiac repair. Here we reassess the lineage tracing data by investigating the identity of cells immediately after Cre labeling. Our instant lineage tracing approach identifies Kit-expressing cardiomyocytes, which are labeled immediately after tamoxifen induction. In combination with long-term lineage tracing experiments, these data reveal that the large majority of long-term labeled cardiomyocytes are pre-existing Kit-expressing cardiomyocytes rather than cardiomyocytes formed de novo from CSCs. This study presents a new interpretation for the contribution of Kit+ cells to cardiomyocytes and shows that Kit genetic lineage tracing over-estimates the cardiogenic activity of Kit+ CSCs. PMID:26634606

The Genetic Programming of Industrial Microorganisms.

ERIC Educational Resources Information Center

Hopwood, David A.

1981-01-01

Traces the development of the field of industrial microbial genetics, describing a range of techniques for genetic programing. Includes a discussion of site-directed mutagenesis, protoplast fusion, and recombinant DNA manipulations. (CS)

Reducing the genetic code induces massive rearrangement of the proteome

PubMed Central

O’Donoghue, Patrick; Prat, Laure; Kucklick, Martin; Schäfer, Johannes G.; Riedel, Katharina; Rinehart, Jesse; Söll, Dieter; Heinemann, Ilka U.

2014-01-01

Expanding the genetic code is an important aim of synthetic biology, but some organisms developed naturally expanded genetic codes long ago over the course of evolution. Less than 1% of all sequenced genomes encode an operon that reassigns the stop codon UAG to pyrrolysine (Pyl), a genetic code variant that results from the biosynthesis of Pyl-tRNAPyl. To understand the selective advantage of genetically encoding more than 20 amino acids, we constructed a markerless tRNAPyl deletion strain of Methanosarcina acetivorans (ΔpylT) that cannot decode UAG as Pyl or grow on trimethylamine. Phenotypic defects in the ΔpylT strain were evident in minimal medium containing methanol. Proteomic analyses of wild type (WT) M. acetivorans and ΔpylT cells identified 841 proteins from >7,000 significant peptides detected by MS/MS. Protein production from UAG-containing mRNAs was verified for 19 proteins. Translation of UAG codons was verified by MS/MS for eight proteins, including identification of a Pyl residue in PylB, which catalyzes the first step of Pyl biosynthesis. Deletion of tRNAPyl globally altered the proteome, leading to >300 differentially abundant proteins. Reduction of the genetic code from 21 to 20 amino acids led to significant down-regulation in translation initiation factors, amino acid metabolism, and methanogenesis from methanol, which was offset by a compensatory (100-fold) up-regulation in dimethyl sulfide metabolic enzymes. The data show how a natural proteome adapts to genetic code reduction and indicate that the selective value of an expanded genetic code is related to carbon source range and metabolic efficiency. PMID:25404328

Ray tracing through a hexahedral mesh in HADES

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

Henderson, G L; Aufderheide, M B

In this paper we describe a new ray tracing method targeted for inclusion in HADES. The algorithm tracks rays through three-dimensional tetrakis hexahedral mesh objects, like those used by the ARES code to model inertial confinement experiments.

Adaptive antioxidant methionine accumulation in respiratory chain complexes explains the use of a deviant genetic code in mitochondria.

PubMed

Bender, Aline; Hajieva, Parvana; Moosmann, Bernd

2008-10-28

Humans and most other animals use 2 different genetic codes to translate their hereditary information: the standard code for nuclear-encoded proteins and a modern variant of this code in mitochondria. Despite the pivotal role of the genetic code for cell biology, the functional significance of the deviant mitochondrial code has remained enigmatic since its first description in 1979. Here, we show that profound and functionally beneficial alterations on the encoded protein level were causative for the AUA codon reassignment from isoleucine to methionine observed in most mitochondrial lineages. We demonstrate that this codon reassignment leads to a massive accumulation of the easily oxidized amino acid methionine in the highly oxidative inner mitochondrial membrane. This apparently paradoxical outcome can yet be smoothly settled if the antioxidant surface chemistry of methionine is taken into account, and we present direct experimental evidence that intramembrane accumulation of methionine exhibits antioxidant and cytoprotective properties in living cells. Our results unveil that methionine is an evolutionarily selected antioxidant building block of respiratory chain complexes. Collective protein alterations can thus constitute the selective advantage behind codon reassignments, which authenticates the "ambiguous decoding" hypothesis of genetic code evolution. Oxidative stress has shaped the mitochondrial genetic code.

Adverb Code-Switching among Miami's Haitian Creole-English Second Generation

ERIC Educational Resources Information Center

Hebblethwaite, Benjamin

2010-01-01

The findings for adverbs and adverbial phrases in a naturalistic corpus of Miami Haitian Creole-English code-switching show that one language, Haitian Creole, asymmetrically supplies the grammatical frame while the other language, English, asymmetrically supplies mixed lexical categories like adverbs. Traces of code-switching with an English frame…

Coding of Stimuli by Animals: Retrospection, Prospection, Episodic Memory and Future Planning

ERIC Educational Resources Information Center

Zentall, Thomas R.

2010-01-01

When animals code stimuli for later retrieval they can either code them in terms of the stimulus presented (as a retrospective memory) or in terms of the response or outcome anticipated (as a prospective memory). Although retrospective memory is typically assumed (as in the form of a memory trace), evidence of prospective coding has been found…

Bioinformatic Analysis Reveals Archaeal tRNATyr and tRNATrp Identities in Bacteria

PubMed Central

Mukai, Takahito; Reynolds, Noah M.; Crnković, Ana; Söll, Dieter

2017-01-01

The tRNA identity elements for some amino acids are distinct between the bacterial and archaeal domains. Searching in recent genomic and metagenomic sequence data, we found some candidate phyla radiation (CPR) bacteria with archaeal tRNA identity for Tyr-tRNA and Trp-tRNA synthesis. These bacteria possess genes for tyrosyl-tRNA synthetase (TyrRS) and tryptophanyl-tRNA synthetase (TrpRS) predicted to be derived from DPANN superphylum archaea, while the cognate tRNATyr and tRNATrp genes reveal bacterial or archaeal origins. We identified a trace of domain fusion and swapping in the archaeal-type TyrRS gene of a bacterial lineage, suggesting that CPR bacteria may have used this mechanism to create diverse proteins. Archaeal-type TrpRS of bacteria and a few TrpRS species of DPANN archaea represent a new phylogenetic clade (named TrpRS-A). The TrpRS-A open reading frames (ORFs) are always associated with another ORF (named ORF1) encoding an unknown protein without global sequence identity to any known protein. However, our protein structure prediction identified a putative HIGH-motif and KMSKS-motif as well as many α-helices that are characteristic of class I aminoacyl-tRNA synthetase (aaRS) homologs. These results provide another example of the diversity of molecular components that implement the genetic code and provide a clue to the early evolution of life and the genetic code. PMID:28230768

Towards a Consolidated Approach for the Assessment of Evaluation Models of Nuclear Power Reactors

DOE PAGES

Epiney, A.; Canepa, S.; Zerkak, O.; ...

2016-11-02

The STARS project at the Paul Scherrer Institut (PSI) has adopted the TRACE thermal-hydraulic (T-H) code for best-estimate system transient simulations of the Swiss Light Water Reactors (LWRs). For analyses involving interactions between system and core, a coupling of TRACE with the SIMULATE-3K (S3K) LWR core simulator has also been developed. In this configuration, the TRACE code and associated nuclear power reactor simulation models play a central role to achieve a comprehensive safety analysis capability. Thus, efforts have now been undertaken to consolidate the validation strategy by implementing a more rigorous and structured assessment approach for TRACE applications involving eithermore » only system T-H evaluations or requiring interfaces to e.g. detailed core or fuel behavior models. The first part of this paper presents the preliminary concepts of this validation strategy. The principle is to systematically track the evolution of a given set of predicted physical Quantities of Interest (QoIs) over a multidimensional parametric space where each of the dimensions represent the evolution of specific analysis aspects, including e.g. code version, transient specific simulation methodology and model "nodalisation". If properly set up, such environment should provide code developers and code users with persistent (less affected by user effect) and quantified information (sensitivity of QoIs) on the applicability of a simulation scheme (codes, input models, methodology) for steady state and transient analysis of full LWR systems. Through this, for each given transient/accident, critical paths of the validation process can be identified that could then translate into defining reference schemes to be applied for downstream predictive simulations. In order to illustrate this approach, the second part of this paper presents a first application of this validation strategy to an inadvertent blowdown event that occurred in a Swiss BWR/6. The transient was initiated by the spurious actuation of the Automatic Depressurization System (ADS). The validation approach progresses through a number of dimensions here: First, the same BWR system simulation model is assessed for different versions of the TRACE code, up to the most recent one. The second dimension is the "nodalisation" dimension, where changes to the input model are assessed. The third dimension is the "methodology" dimension. In this case imposed power and an updated TRACE core model are investigated. For each step in each validation dimension, a common set of QoIs are investigated. For the steady-state results, these include fuel temperatures distributions. For the transient part of the present study, the evaluated QoIs include the system pressure evolution and water carry-over into the steam line.« less

Stop Codon Reassignment in the Wild

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

Ivanova, Natalia; Schwientek, Patrick; Tripp, H. James

Since the discovery of the genetic code and protein translation mechanisms (1), a limited number of variations of the standard assignment between unique base triplets (codons) and their encoded amino acids and translational stop signals have been found in bacteria and phages (2-3). Given the apparent ubiquity of the canonical genetic code, the design of genomically recoded organisms with non-canonical codes has been suggested as a means to prevent horizontal gene transfer between laboratory and environmental organisms (4). It is also predicted that genomically recoded organisms are immune to infection by viruses, under the assumption that phages and their hostsmore » must share a common genetic code (5). This paradigm is supported by the observation of increased resistance of genomically recoded bacteria to phages with a canonical code (4). Despite these assumptions and accompanying lines of evidence, it remains unclear whether differential and non-canonical codon usage represents an absolute barrier to phage infection and genetic exchange between organisms. Our knowledge of the diversity of genetic codes and their use by viruses and their hosts is primarily derived from the analysis of cultivated organisms. Advances in single-cell sequencing and metagenome assembly technologies have enabled the reconstruction of genomes of uncultivated bacterial and archaeal lineages (6). These initial findings suggest that large scale systematic studies of uncultivated microorganisms and viruses may reveal the extent and modes of divergence from the canonical genetic code operating in nature. To explore alternative genetic codes, we carried out a systematic analysis of stop codon reassignments from the canonical TAG amber, TGA opal, and TAA ochre codons in assembled metagenomes from environmental and host-associated samples, single-cell genomes of uncultivated bacteria and archaea, and a collection of phage sequences« less

Genetic origin, admixture, and asymmetry in maternal and paternal human lineages in Cuba

PubMed Central

2008-01-01

Background Before the arrival of Europeans to Cuba, the island was inhabited by two Native American groups, the Tainos and the Ciboneys. Most of the present archaeological, linguistic and ancient DNA evidence indicates a South American origin for these populations. In colonial times, Cuban Native American people were replaced by European settlers and slaves from Africa. It is still unknown however, to what extent their genetic pool intermingled with and was 'diluted' by the arrival of newcomers. In order to investigate the demographic processes that gave rise to the current Cuban population, we analyzed the hypervariable region I (HVS-I) and five single nucleotide polymorphisms (SNPs) in the mitochondrial DNA (mtDNA) coding region in 245 individuals, and 40 Y-chromosome SNPs in 132 male individuals. Results The Native American contribution to present-day Cubans accounted for 33% of the maternal lineages, whereas Africa and Eurasia contributed 45% and 22% of the lineages, respectively. This Native American substrate in Cuba cannot be traced back to a single origin within the American continent, as previously suggested by ancient DNA analyses. Strikingly, no Native American lineages were found for the Y-chromosome, for which the Eurasian and African contributions were around 80% and 20%, respectively. Conclusion While the ancestral Native American substrate is still appreciable in the maternal lineages, the extensive process of population admixture in Cuba has left no trace of the paternal Native American lineages, mirroring the strong sexual bias in the admixture processes taking place during colonial times. PMID:18644108

The Evolution of Random Number Generation in MUVES

DTIC Science & Technology

2017-01-01

mathematical basis and statistical justification for algorithms used in the code. The working code provided produces results identical to the current...MUVES, includ- ing the mathematical basis and statistical justification for algorithms used in the code. The working code provided produces results...questionable numerical and statistical properties. The development of the modern system is traced through software change requests, resulting in a random number

The fourfold way of the genetic code.

PubMed

Jiménez-Montaño, Miguel Angel

2009-11-01

We describe a compact representation of the genetic code that factorizes the table in quartets. It represents a "least grammar" for the genetic language. It is justified by the Klein-4 group structure of RNA bases and codon doublets. The matrix of the outer product between the column-vector of bases and the corresponding row-vector V(T)=(C G U A), considered as signal vectors, has a block structure consisting of the four cosets of the KxK group of base transformations acting on doublet AA. This matrix, translated into weak/strong (W/S) and purine/pyrimidine (R/Y) nucleotide classes, leads to a code table with mixed and unmixed families in separate regions. A basic difference between them is the non-commuting (R/Y) doublets: AC/CA, GU/UG. We describe the degeneracy in the canonical code and the systematic changes in deviant codes in terms of the divisors of 24, employing modulo multiplication groups. We illustrate binary sub-codes characterizing mutations in the quartets. We introduce a decision-tree to predict the mode of tRNA recognition corresponding to each codon, and compare our result with related findings by Jestin and Soulé [Jestin, J.-L., Soulé, C., 2007. Symmetries by base substitutions in the genetic code predict 2' or 3' aminoacylation of tRNAs. J. Theor. Biol. 247, 391-394], and the rearrangements of the table by Delarue [Delarue, M., 2007. An asymmetric underlying rule in the assignment of codons: possible clue to a quick early evolution of the genetic code via successive binary choices. RNA 13, 161-169] and Rodin and Rodin [Rodin, S.N., Rodin, A.S., 2008. On the origin of the genetic code: signatures of its primordial complementarity in tRNAs and aminoacyl-tRNA synthetases. Heredity 100, 341-355], respectively.

A three-dimensional spacecraft-charging computer code

NASA Technical Reports Server (NTRS)

Rubin, A. G.; Katz, I.; Mandell, M.; Schnuelle, G.; Steen, P.; Parks, D.; Cassidy, J.; Roche, J.

1980-01-01

A computer code is described which simulates the interaction of the space environment with a satellite at geosynchronous altitude. Employing finite elements, a three-dimensional satellite model has been constructed with more than 1000 surface cells and 15 different surface materials. Free space around the satellite is modeled by nesting grids within grids. Applications of this NASA Spacecraft Charging Analyzer Program (NASCAP) code to the study of a satellite photosheath and the differential charging of the SCATHA (satellite charging at high altitudes) satellite in eclipse and in sunlight are discussed. In order to understand detector response when the satellite is charged, the code is used to trace the trajectories of particles reaching the SCATHA detectors. Particle trajectories from positive and negative emitters on SCATHA also are traced to determine the location of returning particles, to estimate the escaping flux, and to simulate active control of satellite potentials.

CMCpy: Genetic Code-Message Coevolution Models in Python

PubMed Central

Becich, Peter J.; Stark, Brian P.; Bhat, Harish S.; Ardell, David H.

2013-01-01

Code-message coevolution (CMC) models represent coevolution of a genetic code and a population of protein-coding genes (“messages”). Formally, CMC models are sets of quasispecies coupled together for fitness through a shared genetic code. Although CMC models display plausible explanations for the origin of multiple genetic code traits by natural selection, useful modern implementations of CMC models are not currently available. To meet this need we present CMCpy, an object-oriented Python API and command-line executable front-end that can reproduce all published results of CMC models. CMCpy implements multiple solvers for leading eigenpairs of quasispecies models. We also present novel analytical results that extend and generalize applications of perturbation theory to quasispecies models and pioneer the application of a homotopy method for quasispecies with non-unique maximally fit genotypes. Our results therefore facilitate the computational and analytical study of a variety of evolutionary systems. CMCpy is free open-source software available from http://pypi.python.org/pypi/CMCpy/. PMID:23532367

The evolution of the genetic code: Impasses and challenges.

PubMed

Kun, Ádám; Radványi, Ádám

2018-02-01

The origin of the genetic code and translation is a "notoriously difficult problem". In this survey we present a list of questions that a full theory of the genetic code needs to answer. We assess the leading hypotheses according to these criteria. The stereochemical, the coding coenzyme handle, the coevolution, the four-column theory, the error minimization and the frozen accident hypotheses are discussed. The integration of these hypotheses can account for the origin of the genetic code. But experiments are badly needed. Thus we suggest a host of experiments that could (in)validate some of the models. We focus especially on the coding coenzyme handle hypothesis (CCH). The CCH suggests that amino acids attached to RNA handles enhanced catalytic activities of ribozymes. Alternatively, amino acids without handles or with a handle consisting of a single adenine, like in contemporary coenzymes could have been employed. All three scenarios can be tested in in vitro compartmentalized systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Teleology and teleonomy in behavior analysis

PubMed Central

Reese, Hayne W.

1994-01-01

Teleological descriptions and explanations refer to purpose as consequent to a phenomenon. They become nonteleological if purpose is represented as antecedent to the phenomenon. Such nonteleological statements are called teleonomic, especially when they refer to antecedent genetic “programs.” In behavior analysis, purpose is attributed to the organism's history of consequences. Such a history may leave a trace—physiological (mechanism) or mental (cognitivism)—or the issue of traces may be irrelevant (contextualism). The history or trace is antecedent to current responding, and thus is not a teleological concept in the classical sense. It could be called a teleonomic concept, but this designation is undesirable if it implies exclusively genetic programming, because the history or trace is genetically programmed in evolutionary selection but not in ontogenetic selection. Therefore, the concepts of teleology and teleonomy are not useful for behavior analysis, and invoking them can be misleading. The concept of purpose can be useful if it is not reified. PMID:22478174

Genetic coding and gene expression - new Quadruplet genetic coding model

NASA Astrophysics Data System (ADS)

Shankar Singh, Rama

2012-07-01

Successful demonstration of human genome project has opened the door not only for developing personalized medicine and cure for genetic diseases, but it may also answer the complex and difficult question of the origin of life. It may lead to making 21st century, a century of Biological Sciences as well. Based on the central dogma of Biology, genetic codons in conjunction with tRNA play a key role in translating the RNA bases forming sequence of amino acids leading to a synthesized protein. This is the most critical step in synthesizing the right protein needed for personalized medicine and curing genetic diseases. So far, only triplet codons involving three bases of RNA, transcribed from DNA bases, have been used. Since this approach has several inconsistencies and limitations, even the promise of personalized medicine has not been realized. The new Quadruplet genetic coding model proposed and developed here involves all four RNA bases which in conjunction with tRNA will synthesize the right protein. The transcription and translation process used will be the same, but the Quadruplet codons will help overcome most of the inconsistencies and limitations of the triplet codes. Details of this new Quadruplet genetic coding model and its subsequent potential applications including relevance to the origin of life will be presented.

Carbon source-dependent expansion of the genetic code in bacteria

PubMed Central

Prat, Laure; Heinemann, Ilka U.; Aerni, Hans R.; Rinehart, Jesse; O’Donoghue, Patrick; Söll, Dieter

2012-01-01

Despite the fact that the genetic code is known to vary between organisms in rare cases, it is believed that in the lifetime of a single cell the code is stable. We found Acetohalobium arabaticum cells grown on pyruvate genetically encode 20 amino acids, but in the presence of trimethylamine (TMA), A. arabaticum dynamically expands its genetic code to 21 amino acids including pyrrolysine (Pyl). A. arabaticum is the only known organism that modulates the size of its genetic code in response to its environment and energy source. The gene cassette pylTSBCD, required to biosynthesize and genetically encode UAG codons as Pyl, is present in the genomes of 24 anaerobic archaea and bacteria. Unlike archaeal Pyl-decoding organisms that constitutively encode Pyl, we observed that A. arabaticum controls Pyl encoding by down-regulating transcription of the entire Pyl operon under growth conditions lacking TMA, to the point where no detectable Pyl-tRNAPyl is made in vivo. Pyl-decoding archaea adapted to an expanded genetic code by minimizing TAG codon frequency to typically ∼5% of ORFs, whereas Pyl-decoding bacteria (∼20% of ORFs contain in-frame TAGs) regulate Pyl-tRNAPyl formation and translation of UAG by transcriptional deactivation of genes in the Pyl operon. We further demonstrate that Pyl encoding occurs in a bacterium that naturally encodes the Pyl operon, and identified Pyl residues by mass spectrometry in A. arabaticum proteins including two methylamine methyltransferases. PMID:23185002

HIV-TRACE (Transmission Cluster Engine): a tool for large scale molecular epidemiology of HIV-1 and other rapidly evolving pathogens.

PubMed

Kosakovsky Pond, Sergei L; Weaver, Steven; Leigh Brown, Andrew J; Wertheim, Joel O

2018-01-31

In modern applications of molecular epidemiology, genetic sequence data are routinely used to identify clusters of transmission in rapidly evolving pathogens, most notably HIV-1. Traditional 'shoeleather' epidemiology infers transmission clusters by tracing chains of partners sharing epidemiological connections (e.g., sexual contact). Here, we present a computational tool for identifying a molecular transmission analog of such clusters: HIV-TRACE (TRAnsmission Cluster Engine). HIV-TRACE implements an approach inspired by traditional epidemiology, by identifying chains of partners whose viral genetic relatedness imply direct or indirect epidemiological connections. Molecular transmission clusters are constructed using codon-aware pairwise alignment to a reference sequence followed by pairwise genetic distance estimation among all sequences. This approach is computationally tractable and is capable of identifying HIV-1 transmission clusters in large surveillance databases comprising tens or hundreds of thousands of sequences in near real time, i.e., on the order of minutes to hours. HIV-TRACE is available at www.hivtrace.org and from github.com/veg/hivtrace, along with the accompanying result visualization module from github.com/veg/hivtrace-viz. Importantly, the approach underlying HIV-TRACE is not limited to the study of HIV-1 and can be applied to study outbreaks and epidemics of other rapidly evolving pathogens. © The Author 2018. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Question 6: coevolution theory of the genetic code: a proven theory.

PubMed

Wong, Jeffrey Tze-Fei

2007-10-01

The coevolution theory proposes that primordial proteins consisted only of those amino acids readily obtainable from the prebiotic environment, representing about half the twenty encoded amino acids of today, and the missing amino acids entered the system as the code expanded along with pathways of amino acid biosynthesis. The isolation of genetic code mutants, and the antiquity of pretran synthesis revealed by the comparative genomics of tRNAs and aminoacyl-tRNA synthetases, have combined to provide a rigorous proof of the four fundamental tenets of the theory, thus solving the riddle of the structure of the universal genetic code.

Historical Roots and Future Perspectives Related to Nursing Ethics.

ERIC Educational Resources Information Center

Freitas, Lorraine

1990-01-01

This article traces the evolution of the development and refinement of the professional code from concerns about the ethical conduct of nurses to its present state as a professional code for all nurses. The relationship of the Ethics Committee of the American Nurses' Association to the development of the code is also discussed. (Author/MLW)

Steady State Film Boiling Heat Transfer Simulated With Trace V4.160

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

Audrius Jasiulevicius; Rafael Macian-Juan

2006-07-01

This paper presents the results of the assessment and analysis of TRACE v4.160 heat transfer predictions in the post-CHF (critical heat flux) region and discusses the possibilities to improve the TRACE v4.160 code predictions in the film boiling heat transfer when applying different film boiling correlations. For this purpose, the TRACE v4.160-calculated film boiling heat flux and the resulting maximum inner wall temperatures during film boiling in single tubes were compared with experimental data obtained at the Royal Institute of Technology (KTH) in Stockholm, Sweden. The experimental database included measurements for pressures ranging from 30 to 200 bar and coolantmore » mass fluxes from 500 to 3000 kg/m{sup 2}s. It was found that TRACE v4.160 does not produce correct predictions of the film boiling heat flux, and consequently of the maximum inner wall temperature in the test section, under the wide range of conditions documented in the KTH experiments. In particular, it was found that the standard TRACE v4.160 under-predicts the film boiling heat transfer coefficient at low pressure-low mass flux and high pressure-high mass flux conditions. For most of the rest of the investigated range of parameters, TRACE v4.160 over-predicts the film boiling heat transfer coefficient, which can lead to non-conservative predictions in applications to nuclear power plant analyses. Since no satisfactory agreement with the experimental database was obtained with the standard TRACE v4.160 film boiling heat transfer correlations, we have added seven film boiling correlations to TRACE v4.160 in order to investigate the possibility to improve the code predictions for the conditions similar to the KTH tests. The film boiling correlations were selected among the most commonly used film boiling correlations found in the open literature, namely Groeneveld 5.7, Bishop (2 correlations), Tong, Konkov, Miropolskii and Groeneveld-Delorme correlations. The only correlation among the investigated, which resulted in a significant improvement of TRACE predictions, was the Groeneveld 5.7. It was found, that replacing the current film boiling correlation (Dougall-Rohsenow) for the wall-togas heat transfer with Groeneveld 5.7 improves the code predictions for the film boiling heat transfer at high qualities in single tubes in the entire range of pressure and coolant mass flux considered. (authors)« less

Value-Based Requirements Traceability: Lessons Learned

NASA Astrophysics Data System (ADS)

Egyed, Alexander; Grünbacher, Paul; Heindl, Matthias; Biffl, Stefan

Traceability from requirements to code is mandated by numerous software development standards. These standards, however, are not explicit about the appropriate level of quality of trace links. From a technical perspective, trace quality should meet the needs of the intended trace utilizations. Unfortunately, long-term trace utilizations are typically unknown at the time of trace acquisition which represents a dilemma for many companies. This chapter suggests ways to balance the cost and benefits of requirements traceability. We present data from three case studies demonstrating that trace acquisition requires broad coverage but can tolerate imprecision. With this trade-off our lessons learned suggest a traceability strategy that (1) provides trace links more quickly, (2) refines trace links according to user-defined value considerations, and (3) supports the later refinement of trace links in case the initial value consideration has changed over time. The scope of our work considers the entire life cycle of traceability instead of just the creation of trace links.

Image Tracing: An Analysis of Its Effectiveness in Children's Pictorial Discrimination Learning

ERIC Educational Resources Information Center

Levin, Joel R.; And Others

1977-01-01

A total of 45 fifth grade students were the subjects of an experiment offering support for a component of learning strategy (memory imagery). Various theoretical explanations of the image-tracing phenomenon are considered, including depth of processing, dual coding and frequency. (MS)

Phenotypic Graphs and Evolution Unfold the Standard Genetic Code as the Optimal

NASA Astrophysics Data System (ADS)

Zamudio, Gabriel S.; José, Marco V.

2018-03-01

In this work, we explicitly consider the evolution of the Standard Genetic Code (SGC) by assuming two evolutionary stages, to wit, the primeval RNY code and two intermediate codes in between. We used network theory and graph theory to measure the connectivity of each phenotypic graph. The connectivity values are compared to the values of the codes under different randomization scenarios. An error-correcting optimal code is one in which the algebraic connectivity is minimized. We show that the SGC is optimal in regard to its robustness and error-tolerance when compared to all random codes under different assumptions.

Genetic validation of bipolar disorder identified by automated phenotyping using electronic health records.

PubMed

Chen, Chia-Yen; Lee, Phil H; Castro, Victor M; Minnier, Jessica; Charney, Alexander W; Stahl, Eli A; Ruderfer, Douglas M; Murphy, Shawn N; Gainer, Vivian; Cai, Tianxi; Jones, Ian; Pato, Carlos N; Pato, Michele T; Landén, Mikael; Sklar, Pamela; Perlis, Roy H; Smoller, Jordan W

2018-04-18

Bipolar disorder (BD) is a heritable mood disorder characterized by episodes of mania and depression. Although genomewide association studies (GWAS) have successfully identified genetic loci contributing to BD risk, sample size has become a rate-limiting obstacle to genetic discovery. Electronic health records (EHRs) represent a vast but relatively untapped resource for high-throughput phenotyping. As part of the International Cohort Collection for Bipolar Disorder (ICCBD), we previously validated automated EHR-based phenotyping algorithms for BD against in-person diagnostic interviews (Castro et al. Am J Psychiatry 172:363-372, 2015). Here, we establish the genetic validity of these phenotypes by determining their genetic correlation with traditionally ascertained samples. Case and control algorithms were derived from structured and narrative text in the Partners Healthcare system comprising more than 4.6 million patients over 20 years. Genomewide genotype data for 3330 BD cases and 3952 controls of European ancestry were used to estimate SNP-based heritability (h 2 g ) and genetic correlation (r g ) between EHR-based phenotype definitions and traditionally ascertained BD cases in GWAS by the ICCBD and Psychiatric Genomics Consortium (PGC) using LD score regression. We evaluated BD cases identified using 4 EHR-based algorithms: an NLP-based algorithm (95-NLP) and three rule-based algorithms using codified EHR with decreasing levels of stringency-"coded-strict", "coded-broad", and "coded-broad based on a single clinical encounter" (coded-broad-SV). The analytic sample comprised 862 95-NLP, 1968 coded-strict, 2581 coded-broad, 408 coded-broad-SV BD cases, and 3 952 controls. The estimated h 2 g were 0.24 (p = 0.015), 0.09 (p = 0.064), 0.13 (p = 0.003), 0.00 (p = 0.591) for 95-NLP, coded-strict, coded-broad and coded-broad-SV BD, respectively. The h 2 g for all EHR-based cases combined except coded-broad-SV (excluded due to 0 h 2 g ) was 0.12 (p = 0.004). These h 2 g were lower or similar to the h 2 g observed by the ICCBD + PGCBD (0.23, p = 3.17E-80, total N = 33,181). However, the r g between ICCBD + PGCBD and the EHR-based cases were high for 95-NLP (0.66, p = 3.69 × 10 -5 ), coded-strict (1.00, p = 2.40 × 10 -4 ), and coded-broad (0.74, p = 8.11 × 10 -7 ). The r g between EHR-based BD definitions ranged from 0.90 to 0.98. These results provide the first genetic validation of automated EHR-based phenotyping for BD and suggest that this approach identifies cases that are highly genetically correlated with those ascertained through conventional methods. High throughput phenotyping using the large data resources available in EHRs represents a viable method for accelerating psychiatric genetic research.

Comparison of a 3-D GPU-Assisted Maxwell Code and Ray Tracing for Reflectometry on ITER

NASA Astrophysics Data System (ADS)

Gady, Sarah; Kubota, Shigeyuki; Johnson, Irena

2015-11-01

Electromagnetic wave propagation and scattering in magnetized plasmas are important diagnostics for high temperature plasmas. 1-D and 2-D full-wave codes are standard tools for measurements of the electron density profile and fluctuations; however, ray tracing results have shown that beam propagation in tokamak plasmas is inherently a 3-D problem. The GPU-Assisted Maxwell Code utilizes the FDTD (Finite-Difference Time-Domain) method for solving the Maxwell equations with the cold plasma approximation in a 3-D geometry. Parallel processing with GPGPU (General-Purpose computing on Graphics Processing Units) is used to accelerate the computation. Previously, we reported on initial comparisons of the code results to 1-D numerical and analytical solutions, where the size of the computational grid was limited by the on-board memory of the GPU. In the current study, this limitation is overcome by using domain decomposition and an additional GPU. As a practical application, this code is used to study the current design of the ITER Low Field Side Reflectometer (LSFR) for the Equatorial Port Plug 11 (EPP11). A detailed examination of Gaussian beam propagation in the ITER edge plasma will be presented, as well as comparisons with ray tracing. This work was made possible by funding from the Department of Energy for the Summer Undergraduate Laboratory Internship (SULI) program. This work is supported by the US DOE Contract No.DE-AC02-09CH11466 and DE-FG02-99-ER54527.

Rooted tRNAomes and evolution of the genetic code

PubMed Central

Pak, Daewoo; Du, Nan; Kim, Yunsoo; Sun, Yanni

2018-01-01

ABSTRACT We advocate for a tRNA- rather than an mRNA-centric model for evolution of the genetic code. The mechanism for evolution of cloverleaf tRNA provides a root sequence for radiation of tRNAs and suggests a simplified understanding of code evolution. To analyze code sectoring, rooted tRNAomes were compared for several archaeal and one bacterial species. Rooting of tRNAome trees reveals conserved structures, indicating how the code was shaped during evolution and suggesting a model for evolution of a LUCA tRNAome tree. We propose the polyglycine hypothesis that the initial product of the genetic code may have been short chain polyglycine to stabilize protocells. In order to describe how anticodons were allotted in evolution, the sectoring-degeneracy hypothesis is proposed. Based on sectoring, a simple stepwise model is developed, in which the code sectors from a 1→4→8→∼16 letter code. At initial stages of code evolution, we posit strong positive selection for wobble base ambiguity, supporting convergence to 4-codon sectors and ∼16 letters. In a later stage, ∼5–6 letters, including stops, were added through innovating at the anticodon wobble position. In archaea and bacteria, tRNA wobble adenine is negatively selected, shrinking the maximum size of the primordial genetic code to 48 anticodons. Because 64 codons are recognized in mRNA, tRNA-mRNA coevolution requires tRNA wobble position ambiguity leading to degeneracy of the code. PMID:29372672

The "periodic table" of the genetic code: A new way to look at the code and the decoding process.

PubMed

Komar, Anton A

2016-01-01

Henri Grosjean and Eric Westhof recently presented an information-rich, alternative view of the genetic code, which takes into account current knowledge of the decoding process, including the complex nature of interactions between mRNA, tRNA and rRNA that take place during protein synthesis on the ribosome, and it also better reflects the evolution of the code. The new asymmetrical circular genetic code has a number of advantages over the traditional codon table and the previous circular diagrams (with a symmetrical/clockwise arrangement of the U, C, A, G bases). Most importantly, all sequence co-variances can be visualized and explained based on the internal logic of the thermodynamics of codon-anticodon interactions.

Correlation between Hox code and vertebral morphology in archosaurs.

PubMed

Böhmer, Christine; Rauhut, Oliver W M; Wörheide, Gert

2015-07-07

The relationship between developmental genes and phenotypic variation is of central interest in evolutionary biology. An excellent example is the role of Hox genes in the anteroposterior regionalization of the vertebral column in vertebrates. Archosaurs (crocodiles, dinosaurs including birds) are highly variable both in vertebral morphology and number. Nevertheless, functionally equivalent Hox genes are active in the axial skeleton during embryonic development, indicating that the morphological variation across taxa is likely owing to modifications in the pattern of Hox gene expression. By using geometric morphometrics, we demonstrate a correlation between vertebral Hox code and quantifiable vertebral morphology in modern archosaurs, in which the boundaries between morphological subgroups of vertebrae can be linked to anterior Hox gene expression boundaries. Our findings reveal homologous units of cervical vertebrae in modern archosaurs, each with their specific Hox gene pattern, enabling us to trace these homologies in the extinct sauropodomorph dinosaurs, a group with highly variable vertebral counts. Based on the quantifiable vertebral morphology, this allows us to infer the underlying genetic mechanisms in vertebral evolution in fossils, which represents not only an important case study, but will lead to a better understanding of the origin of morphological disparity in recent archosaur vertebral columns.

Correlation between Hox code and vertebral morphology in archosaurs

PubMed Central

Böhmer, Christine; Rauhut, Oliver W. M.; Wörheide, Gert

2015-01-01

The relationship between developmental genes and phenotypic variation is of central interest in evolutionary biology. An excellent example is the role of Hox genes in the anteroposterior regionalization of the vertebral column in vertebrates. Archosaurs (crocodiles, dinosaurs including birds) are highly variable both in vertebral morphology and number. Nevertheless, functionally equivalent Hox genes are active in the axial skeleton during embryonic development, indicating that the morphological variation across taxa is likely owing to modifications in the pattern of Hox gene expression. By using geometric morphometrics, we demonstrate a correlation between vertebral Hox code and quantifiable vertebral morphology in modern archosaurs, in which the boundaries between morphological subgroups of vertebrae can be linked to anterior Hox gene expression boundaries. Our findings reveal homologous units of cervical vertebrae in modern archosaurs, each with their specific Hox gene pattern, enabling us to trace these homologies in the extinct sauropodomorph dinosaurs, a group with highly variable vertebral counts. Based on the quantifiable vertebral morphology, this allows us to infer the underlying genetic mechanisms in vertebral evolution in fossils, which represents not only an important case study, but will lead to a better understanding of the origin of morphological disparity in recent archosaur vertebral columns. PMID:26085583

Synthetic alienation of microbial organisms by using genetic code engineering: Why and how?

PubMed

Kubyshkin, Vladimir; Budisa, Nediljko

2017-08-01

The main goal of synthetic biology (SB) is the creation of biodiversity applicable for biotechnological needs, while xenobiology (XB) aims to expand the framework of natural chemistries with the non-natural building blocks in living cells to accomplish artificial biodiversity. Protein and proteome engineering, which overcome limitation of the canonical amino acid repertoire of 20 (+2) prescribed by the genetic code by using non-canonic amino acids (ncAAs), is one of the main focuses of XB research. Ideally, estranging the genetic code from its current form via systematic introduction of ncAAs should enable the development of bio-containment mechanisms in synthetic cells potentially endowing them with a "genetic firewall" i.e. orthogonality which prevents genetic information transfer to natural systems. Despite rapid progress over the past two decades, it is not yet possible to completely alienate an organism that would use and maintain different genetic code associations permanently. In order to engineer robust bio-contained life forms, the chemical logic behind the amino acid repertoire establishment should be considered. Starting from recent proposal of Hartman and Smith about the genetic code establishment in the RNA world, here the authors mapped possible biotechnological invasion points for engineering of bio-contained synthetic cells equipped with non-canonical functionalities. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Problem-Based Test: An "In Vitro" Experiment to Analyze the Genetic Code

ERIC Educational Resources Information Center

Szeberenyi, Jozsef

2010-01-01

Terms to be familiar with before you start to solve the test: genetic code, translation, synthetic polynucleotide, leucine, serine, filter precipitation, radioactivity measurement, template, mRNA, tRNA, rRNA, aminoacyl-tRNA synthesis, ribosomes, degeneration of the code, wobble, initiation, and elongation of protein synthesis, initiation codon.…

A Novel Multi-Scale Domain Overlapping CFD/STH Coupling Methodology for Multi-Dimensional Flows Relevant to Nuclear Applications

NASA Astrophysics Data System (ADS)

Grunloh, Timothy P.

The objective of this dissertation is to develop a 3-D domain-overlapping coupling method that leverages the superior flow field resolution of the Computational Fluid Dynamics (CFD) code STAR-CCM+ and the fast execution of the System Thermal Hydraulic (STH) code TRACE to efficiently and accurately model thermal hydraulic transport properties in nuclear power plants under complex conditions of regulatory and economic importance. The primary contribution is the novel Stabilized Inertial Domain Overlapping (SIDO) coupling method, which allows for on-the-fly correction of TRACE solutions for local pressures and velocity profiles inside multi-dimensional regions based on the results of the CFD simulation. The method is found to outperform the more frequently-used domain decomposition coupling methods. An STH code such as TRACE is designed to simulate large, diverse component networks, requiring simplifications to the fluid flow equations for reasonable execution times. Empirical correlations are therefore required for many sub-grid processes. The coarse grids used by TRACE diminish sensitivity to small scale geometric details such as Reactor Pressure Vessel (RPV) internals. A CFD code such as STAR-CCM+ uses much finer computational meshes that are sensitive to the geometric details of reactor internals. In turbulent flows, it is infeasible to fully resolve the flow solution, but the correlations used to model turbulence are at a low level. The CFD code can therefore resolve smaller scale flow processes. The development of a 3-D coupling method was carried out with the intention of improving predictive capabilities of transport properties in the downcomer and lower plenum regions of an RPV in reactor safety calculations. These regions are responsible for the multi-dimensional mixing effects that determine the distribution at the core inlet of quantities with reactivity implications, such as fluid temperature and dissolved neutron absorber concentration.

Method for rapid high-frequency seismogram calculation

NASA Astrophysics Data System (ADS)

Stabile, Tony Alfredo; De Matteis, Raffaella; Zollo, Aldo

2009-02-01

We present a method for rapid, high-frequency seismogram calculation that makes use of an algorithm to automatically generate an exhaustive set of seismic phases with an appreciable amplitude on the seismogram. The method uses a hierarchical order of ray and seismic-phase generation, taking into account some existing constraints for ray paths and some physical constraints. To compute synthetic seismograms, the COMRAD code (from the Italian: "COdice Multifase per il RAy-tracing Dinamico") uses as core a dynamic ray-tracing code. To validate the code, we have computed in a layered medium synthetic seismograms using both COMRAD and a code that computes the complete wave field by the discrete wave number method. The seismograms are compared according to a time-frequency misfit criteria based on the continuous wavelet transform of the signals. Although the number of phases is considerably reduced by the selection criteria, the results show that the loss in amplitude on the whole seismogram is negligible. Moreover, the time for the computing of the synthetics using the COMRAD code (truncating the ray series at the 10th generation) is 3-4-fold less than that needed for the AXITRA code (up to a frequency of 25 Hz).

Population dynamics coded in DNA: genetic traces of the expansion of modern humans

NASA Astrophysics Data System (ADS)

Kimmel, Marek

1999-12-01

It has been proposed that modern humans evolved from a small ancestral population, which appeared several hundred thousand years ago in Africa. Descendants of the founder group migrated to Europe and then to Asia, not mixing with the pre-existing local populations but replacing them. Two demographic elements are present in this “out of Africa” hypothesis: numerical growth of the modern humans and their migration into Eurasia. Did these processes leave an imprint in our DNA? To address this question, we use the classical Fisher-Wright-Moran model of population genetics, assuming variable population size and two models of mutation: the infinite-sites model and the stepwise-mutation model. We use the coalescence theory, which amounts to tracing the common ancestors of contemporary genes. We obtain mathematical formulae expressing the distribution of alleles given the time changes of population size . In the framework of the infinite-sites model, simulations indicate that the pattern of past population size change leaves its signature on the pattern of DNA polymorphism. Application of the theory to the published mitochondrial DNA sequences indicates that the current mitochondrial DNA sequence variation is not inconsistent with the logistic growth of the modern human population. In the framework of the stepwise-mutation model, we demonstrate that population bottleneck followed by growth in size causes an imbalance between allele-size variance and heterozygosity. We analyze a set of data on tetranucleotide repeats which reveals the existence of this imbalance. The pattern of imbalance is consistent with the bottleneck being most ancient in Africans, most recent in Asians and intermediate in Europeans. These findings are consistent with the “out of Africa” hypothesis, although by no means do they constitute its proof.

An extension of the coevolution theory of the origin of the genetic code

PubMed Central

Di Giulio, Massimo

2008-01-01

Background The coevolution theory of the origin of the genetic code suggests that the genetic code is an imprint of the biosynthetic relationships between amino acids. However, this theory does not seem to attribute a role to the biosynthetic relationships between the earliest amino acids that evolved along the pathways of energetic metabolism. As a result, the coevolution theory is unable to clearly define the very earliest phases of genetic code origin. In order to remove this difficulty, I here suggest an extension of the coevolution theory that attributes a crucial role to the first amino acids that evolved along these biosynthetic pathways and to their biosynthetic relationships, even when defined by the non-amino acid molecules that are their precursors. Results It is re-observed that the first amino acids to evolve along these biosynthetic pathways are predominantly those codified by codons of the type GNN, and this observation is found to be statistically significant. Furthermore, the close biosynthetic relationships between the sibling amino acids Ala-Ser, Ser-Gly, Asp-Glu, and Ala-Val are not random in the genetic code table and reinforce the hypothesis that the biosynthetic relationships between these six amino acids played a crucial role in defining the very earliest phases of genetic code origin. Conclusion All this leads to the hypothesis that there existed a code, GNS, reflecting the biosynthetic relationships between these six amino acids which, as it defines the very earliest phases of genetic code origin, removes the main difficulty of the coevolution theory. Furthermore, it is here discussed how this code might have naturally led to the code codifying only for the domains of the codons of precursor amino acids, as predicted by the coevolution theory. Finally, the hypothesis here suggested also removes other problems of the coevolution theory, such as the existence for certain pairs of amino acids with an unclear biosynthetic relationship between the precursor and product amino acids and the collocation of Ala between the amino acids Val and Leu belonging to the pyruvate biosynthetic family, which the coevolution theory considered as belonging to different biosyntheses. Reviewers This article was reviewed by Rob Knight, Paul Higgs (nominated by Laura Landweber), and Eugene Koonin. PMID:18775066

Coupling extended magnetohydrodynamic fluid codes with radiofrequency ray tracing codes for fusion modeling

NASA Astrophysics Data System (ADS)

Jenkins, Thomas G.; Held, Eric D.

2015-09-01

Neoclassical tearing modes are macroscopic (L ∼ 1 m) instabilities in magnetic fusion experiments; if unchecked, these modes degrade plasma performance and may catastrophically destroy plasma confinement by inducing a disruption. Fortunately, the use of properly tuned and directed radiofrequency waves (λ ∼ 1 mm) can eliminate these modes. Numerical modeling of this difficult multiscale problem requires the integration of separate mathematical models for each length and time scale (Jenkins and Kruger, 2012 [21]); the extended MHD model captures macroscopic plasma evolution while the RF model tracks the flow and deposition of injected RF power through the evolving plasma profiles. The scale separation enables use of the eikonal (ray-tracing) approximation to model the RF wave propagation. In this work we demonstrate a technique, based on methods of computational geometry, for mapping the ensuing RF data (associated with discrete ray trajectories) onto the finite-element/pseudospectral grid that is used to model the extended MHD physics. In the new representation, the RF data can then be used to construct source terms in the equations of the extended MHD model, enabling quantitative modeling of RF-induced tearing mode stabilization. Though our specific implementation uses the NIMROD extended MHD (Sovinec et al., 2004 [22]) and GENRAY RF (Smirnov et al., 1994 [23]) codes, the approach presented can be applied more generally to any code coupling requiring the mapping of ray tracing data onto Eulerian grids.

Differentiation of mixed biological traces in sexual assaults using DNA fragment analysis

PubMed Central

Apostolov, Аleksandar

2014-01-01

During the investigation of sexual abuse, it is not rare that mixed genetic material from two or more persons is detected. In such cases, successful profiling can be achieved using DNA fragment analysis, resulting in individual genetic profiles of offenders and their victims. This has led to an increase in the percentage of identified perpetrators of sexual offenses. The classic and modified genetic models used, allowed us to refine and implement appropriate extraction, polymerase chain reaction and electrophoretic procedures with individual assessment and approach to conducting research. Testing mixed biological traces using DNA fragment analysis appears to be the only opportunity for identifying perpetrators in gang rapes. PMID:26019514

Refactoring the Genetic Code for Increased Evolvability

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

Pines, Gur; Winkler, James D.; Pines, Assaf

ABSTRACT The standard genetic code is robust to mutations during transcription and translation. Point mutations are likely to be synonymous or to preserve the chemical properties of the original amino acid. Saturation mutagenesis experiments suggest that in some cases the best-performing mutant requires replacement of more than a single nucleotide within a codon. These replacements are essentially inaccessible to common error-based laboratory engineering techniques that alter a single nucleotide per mutation event, due to the extreme rarity of adjacent mutations. In this theoretical study, we suggest a radical reordering of the genetic code that maximizes the mutagenic potential of singlemore » nucleotide replacements. We explore several possible genetic codes that allow a greater degree of accessibility to the mutational landscape and may result in a hyperevolvable organism that could serve as an ideal platform for directed evolution experiments. We then conclude by evaluating the challenges of constructing such recoded organisms and their potential applications within the field of synthetic biology. IMPORTANCE The conservative nature of the genetic code prevents bioengineers from efficiently accessing the full mutational landscape of a gene via common error-prone methods. Here, we present two computational approaches to generate alternative genetic codes with increased accessibility. These new codes allow mutational transitions to a larger pool of amino acids and with a greater extent of chemical differences, based on a single nucleotide replacement within the codon, thus increasing evolvability both at the single-gene and at the genome levels. Given the widespread use of these techniques for strain and protein improvement, along with more fundamental evolutionary biology questions, the use of recoded organisms that maximize evolvability should significantly improve the efficiency of directed evolution, library generation, and fitness maximization.« less

Refactoring the Genetic Code for Increased Evolvability

DOE PAGES

Pines, Gur; Winkler, James D.; Pines, Assaf; ...

2017-11-14

ABSTRACT The standard genetic code is robust to mutations during transcription and translation. Point mutations are likely to be synonymous or to preserve the chemical properties of the original amino acid. Saturation mutagenesis experiments suggest that in some cases the best-performing mutant requires replacement of more than a single nucleotide within a codon. These replacements are essentially inaccessible to common error-based laboratory engineering techniques that alter a single nucleotide per mutation event, due to the extreme rarity of adjacent mutations. In this theoretical study, we suggest a radical reordering of the genetic code that maximizes the mutagenic potential of singlemore » nucleotide replacements. We explore several possible genetic codes that allow a greater degree of accessibility to the mutational landscape and may result in a hyperevolvable organism that could serve as an ideal platform for directed evolution experiments. We then conclude by evaluating the challenges of constructing such recoded organisms and their potential applications within the field of synthetic biology. IMPORTANCE The conservative nature of the genetic code prevents bioengineers from efficiently accessing the full mutational landscape of a gene via common error-prone methods. Here, we present two computational approaches to generate alternative genetic codes with increased accessibility. These new codes allow mutational transitions to a larger pool of amino acids and with a greater extent of chemical differences, based on a single nucleotide replacement within the codon, thus increasing evolvability both at the single-gene and at the genome levels. Given the widespread use of these techniques for strain and protein improvement, along with more fundamental evolutionary biology questions, the use of recoded organisms that maximize evolvability should significantly improve the efficiency of directed evolution, library generation, and fitness maximization.« less

Health Benefits of Animal Research: The Mouse in Biomedical Research.

ERIC Educational Resources Information Center

Jonas, Albert M.

1984-01-01

Traces the history of using mice for medical research and discusses the benefits of using these animals for studies in bacteriology, virology, genetics (considering X-linked genetic homologies between mice and humans), molecular biology, immunology, hematology, immune response disorders, oncology, radiobiology, pharmacology, behavior genetics,…

Introductory Laboratory Exercises in Radiobiology

ERIC Educational Resources Information Center

Williams, J. R. Parry; Servant, D. M.

1970-01-01

Describes experiments suitable for introducing use of radioisotopes in biology. Includes demonstrations of tracing food chains, uptake of ions by plants, concentration of elements by insects, tracing photosynthetic reactions, activation analysis of copper, and somatic and genetic effects. Uses autoradiographic and counting techniques. (AL)

TRACE/PARCS analysis of the OECD/NEA Oskarshamn-2 BWR stability benchmark

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

Kozlowski, T.; Downar, T.; Xu, Y.

2012-07-01

On February 25, 1999, the Oskarshamn-2 NPP experienced a stability event which culminated in diverging power oscillations with a decay ratio of about 1.4. The event was successfully modeled by the TRACE/PARCS coupled code system, and further analysis of the event is described in this paper. The results show very good agreement with the plant data, capturing the entire behavior of the transient including the onset of instability, growth of the oscillations (decay ratio) and oscillation frequency. This provides confidence in the prediction of other parameters which are not available from the plant records. The event provides coupled code validationmore » for a challenging BWR stability event, which involves the accurate simulation of neutron kinetics (NK), thermal-hydraulics (TH), and TH/NK. coupling. The success of this work has demonstrated the ability of the 3-D coupled systems code TRACE/PARCS to capture the complex behavior of BWR stability events. The problem was released as an international OECD/NEA benchmark, and it is the first benchmark based on measured plant data for a stability event with a DR greater than one. Interested participants are invited to contact authors for more information. (authors)« less

Methods in Molecular Biology Mouse Genetics: Methods and Protocols | Center for Cancer Research

Cancer.gov

Mouse Genetics: Methods and Protocols provides selected mouse genetic techniques and their application in modeling varieties of human diseases. The chapters are mainly focused on the generation of different transgenic mice to accomplish the manipulation of genes of interest, tracing cell lineages, and modeling human diseases.

Mitochondrial genetic codes evolve to match amino acid requirements of proteins.

PubMed

Swire, Jonathan; Judson, Olivia P; Burt, Austin

2005-01-01

Mitochondria often use genetic codes different from the standard genetic code. Now that many mitochondrial genomes have been sequenced, these variant codes provide the first opportunity to examine empirically the processes that produce new genetic codes. The key question is: Are codon reassignments the sole result of mutation and genetic drift? Or are they the result of natural selection? Here we present an analysis of 24 phylogenetically independent codon reassignments in mitochondria. Although the mutation-drift hypothesis can explain reassignments from stop to an amino acid, we found that it cannot explain reassignments from one amino acid to another. In particular--and contrary to the predictions of the mutation-drift hypothesis--the codon involved in such a reassignment was not rare in the ancestral genome. Instead, such reassignments appear to take place while the codon is in use at an appreciable frequency. Moreover, the comparison of inferred amino acid usage in the ancestral genome with the neutral expectation shows that the amino acid gaining the codon was selectively favored over the amino acid losing the codon. These results are consistent with a simple model of weak selection on the amino acid composition of proteins in which codon reassignments are selected because they compensate for multiple slightly deleterious mutations throughout the mitochondrial genome. We propose that the selection pressure is for reduced protein synthesis cost: most reassignments give amino acids that are less expensive to synthesize. Taken together, our results strongly suggest that mitochondrial genetic codes evolve to match the amino acid requirements of proteins.

PheProb: probabilistic phenotyping using diagnosis codes to improve power for genetic association studies.

PubMed

Sinnott, Jennifer A; Cai, Fiona; Yu, Sheng; Hejblum, Boris P; Hong, Chuan; Kohane, Isaac S; Liao, Katherine P

2018-05-17

Standard approaches for large scale phenotypic screens using electronic health record (EHR) data apply thresholds, such as ≥2 diagnosis codes, to define subjects as having a phenotype. However, the variation in the accuracy of diagnosis codes can impair the power of such screens. Our objective was to develop and evaluate an approach which converts diagnosis codes into a probability of a phenotype (PheProb). We hypothesized that this alternate approach for defining phenotypes would improve power for genetic association studies. The PheProb approach employs unsupervised clustering to separate patients into 2 groups based on diagnosis codes. Subjects are assigned a probability of having the phenotype based on the number of diagnosis codes. This approach was developed using simulated EHR data and tested in a real world EHR cohort. In the latter, we tested the association between low density lipoprotein cholesterol (LDL-C) genetic risk alleles known for association with hyperlipidemia and hyperlipidemia codes (ICD-9 272.x). PheProb and thresholding approaches were compared. Among n = 1462 subjects in the real world EHR cohort, the threshold-based p-values for association between the genetic risk score (GRS) and hyperlipidemia were 0.126 (≥1 code), 0.123 (≥2 codes), and 0.142 (≥3 codes). The PheProb approach produced the expected significant association between the GRS and hyperlipidemia: p = .001. PheProb improves statistical power for association studies relative to standard thresholding approaches by leveraging information about the phenotype in the billing code counts. The PheProb approach has direct applications where efficient approaches are required, such as in Phenome-Wide Association Studies.

Detecting Runtime Anomalies in AJAX Applications through Trace Analysis

DTIC Science & Technology

2011-08-10

statements by adding the instrumentation to the GWT UI classes, leaving the user code untouched. Some content management frameworks such as Drupal [12...Google web toolkit.” http://code.google.com/webtoolkit/. [12] “Form generation – drupal api.” http://api.drupal.org/api/group/form_api/6. 9

Experimental studies related to the origin of the genetic code and the process of protein synthesis - A review

NASA Technical Reports Server (NTRS)

Lacey, J. C., Jr.; Mullins, D. W., Jr.

1983-01-01

A survey is presented of the literature on the experimental evidence for the genetic code assignments and the chemical reactions involved in the process of protein synthesis. In view of the enormous number of theoretical models that have been advanced to explain the origin of the genetic code, attention is confined to experimental studies. Since genetic coding has significance only within the context of protein synthesis, it is believed that the problem of the origin of the code must be dealt with in terms of the origin of the process of protein synthesis. It is contended that the answers must lie in the nature of the molecules, amino acids and nucleotides, the affinities they might have for one another, and the effect that those affinities must have on the chemical reactions that are related to primitive protein synthesis. The survey establishes that for the bulk of amino acids, there is a direct and significant correlation between the hydrophobicity rank of the amino acids and the hydrophobicity rank of their anticodonic dinucleotides.

The role of crossover operator in evolutionary-based approach to the problem of genetic code optimization.

PubMed

Błażej, Paweł; Wnȩtrzak, Małgorzata; Mackiewicz, Paweł

2016-12-01

One of theories explaining the present structure of canonical genetic code assumes that it was optimized to minimize harmful effects of amino acid replacements resulting from nucleotide substitutions and translational errors. A way to testify this concept is to find the optimal code under given criteria and compare it with the canonical genetic code. Unfortunately, the huge number of possible alternatives makes it impossible to find the optimal code using exhaustive methods in sensible time. Therefore, heuristic methods should be applied to search the space of possible solutions. Evolutionary algorithms (EA) seem to be ones of such promising approaches. This class of methods is founded both on mutation and crossover operators, which are responsible for creating and maintaining the diversity of candidate solutions. These operators possess dissimilar characteristics and consequently play different roles in the process of finding the best solutions under given criteria. Therefore, the effective searching for the potential solutions can be improved by applying both of them, especially when these operators are devised specifically for a given problem. To study this subject, we analyze the effectiveness of algorithms for various combinations of mutation and crossover probabilities under three models of the genetic code assuming different restrictions on its structure. To achieve that, we adapt the position based crossover operator for the most restricted model and develop a new type of crossover operator for the more general models. The applied fitness function describes costs of amino acid replacement regarding their polarity. Our results indicate that the usage of crossover operators can significantly improve the quality of the solutions. Moreover, the simulations with the crossover operator optimize the fitness function in the smaller number of generations than simulations without this operator. The optimal genetic codes without restrictions on their structure minimize the costs about 2.7 times better than the canonical genetic code. Interestingly, the optimal codes are dominated by amino acids characterized by polarity close to its average value for all amino acids. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Real coded genetic algorithm for fuzzy time series prediction

NASA Astrophysics Data System (ADS)

Jain, Shilpa; Bisht, Dinesh C. S.; Singh, Phool; Mathpal, Prakash C.

2017-10-01

Genetic Algorithm (GA) forms a subset of evolutionary computing, rapidly growing area of Artificial Intelligence (A.I.). Some variants of GA are binary GA, real GA, messy GA, micro GA, saw tooth GA, differential evolution GA. This research article presents a real coded GA for predicting enrollments of University of Alabama. Data of Alabama University is a fuzzy time series. Here, fuzzy logic is used to predict enrollments of Alabama University and genetic algorithm optimizes fuzzy intervals. Results are compared to other eminent author works and found satisfactory, and states that real coded GA are fast and accurate.

Defragged Binary I Ching Genetic Code Chromosomes Compared to Nirenberg’s and Transformed into Rotating 2D Circles and Squares and into a 3D 100% Symmetrical Tetrahedron Coupled to a Functional One to Discern Start From Non-Start Methionines through a Stella Octangula

PubMed Central

Castro-Chavez, Fernando

2012-01-01

Background Three binary representations of the genetic code according to the ancient I Ching of Fu-Xi will be presented, depending on their defragging capabilities by pairing based on three biochemical properties of the nucleic acids: H-bonds, Purine/Pyrimidine rings, and the Keto-enol/Amino-imino tautomerism, yielding the last pair a 32/32 single-strand self-annealed genetic code and I Ching tables. Methods Our working tool is the ancient binary I Ching's resulting genetic code chromosomes defragged by vertical and by horizontal pairing, reverse engineered into non-binaries of 2D rotating 4×4×4 circles and 8×8 squares and into one 3D 100% symmetrical 16×4 tetrahedron coupled to a functional tetrahedron with apical signaling and central hydrophobicity (codon formula: 4[1(1)+1(3)+1(4)+4(2)]; 5:5, 6:6 in man) forming a stella octangula, and compared to Nirenberg's 16×4 codon table (1965) pairing the first two nucleotides of the 64 codons in axis y. Results One horizontal and one vertical defragging had the start Met at the center. Two, both horizontal and vertical pairings produced two pairs of 2×8×4 genetic code chromosomes naturally arranged (M and I), rearranged by semi-introversion of central purines or pyrimidines (M' and I') and by clustering hydrophobic amino acids; their quasi-identity was disrupted by amino acids with odd codons (Met and Tyr pairing to Ile and TGA Stop); in all instances, the 64-grid 90° rotational ability was restored. Conclusions We defragged three I Ching representations of the genetic code while emphasizing Nirenberg's historical finding. The synthetic genetic code chromosomes obtained reflect the protective strategy of enzymes with a similar function, having both humans and mammals a biased G-C dominance of three H-bonds in the third nucleotide of their most used codons per amino acid, as seen in one chromosome of the i, M and M' genetic codes, while a two H-bond A-T dominance was found in their complementary chromosome, as seen in invertebrates and plants. The reverse engineering of chromosome I' into 2D rotating circles and squares was undertaken, yielding a 100% symmetrical 3D geometry which was coupled to a previously obtained genetic code tetrahedron in order to differentiate the start methionine from the methionine that is acting as a codifying non-start codon. PMID:23431415

Common Gene Variants Account for Most Genetic Risk for Autism

MedlinePlus

... gene variants account for most genetic risk for autism Roles of heritability, mutations, environment estimated – NIH-funded study. The bulk of risk, or liability, for autism spectrum disorders (ASD) was traced to inherited variations ...

Tracing the genetic origin of Europe's first farmers reveals insights into their social organization

PubMed Central

Szécsényi-Nagy, Anna; Brandt, Guido; Haak, Wolfgang; Keerl, Victoria; Jakucs, János; Möller-Rieker, Sabine; Köhler, Kitti; Mende, Balázs Gusztáv; Oross, Krisztián; Marton, Tibor; Osztás, Anett; Kiss, Viktória; Fecher, Marc; Pálfi, György; Molnár, Erika; Sebők, Katalin; Czene, András; Paluch, Tibor; Šlaus, Mario; Novak, Mario; Pećina-Šlaus, Nives; Ősz, Brigitta; Voicsek, Vanda; Somogyi, Krisztina; Tóth, Gábor; Kromer, Bernd; Bánffy, Eszter; Alt, Kurt W.

2015-01-01

Farming was established in Central Europe by the Linearbandkeramik culture (LBK), a well-investigated archaeological horizon, which emerged in the Carpathian Basin, in today's Hungary. However, the genetic background of the LBK genesis is yet unclear. Here we present 9 Y chromosomal and 84 mitochondrial DNA profiles from Mesolithic, Neolithic Starčevo and LBK sites (seventh/sixth millennia BC) from the Carpathian Basin and southeastern Europe. We detect genetic continuity of both maternal and paternal elements during the initial spread of agriculture, and confirm the substantial genetic impact of early southeastern European and Carpathian Basin farming cultures on Central European populations of the sixth–fourth millennia BC. Comprehensive Y chromosomal and mitochondrial DNA population genetic analyses demonstrate a clear affinity of the early farmers to the modern Near East and Caucasus, tracing the expansion from that region through southeastern Europe and the Carpathian Basin into Central Europe. However, our results also reveal contrasting patterns for male and female genetic diversity in the European Neolithic, suggesting a system of patrilineal descent and patrilocal residential rules among the early farmers. PMID:25808890

Quaternionic representation of the genetic code.

PubMed

Carlevaro, C Manuel; Irastorza, Ramiro M; Vericat, Fernando

2016-03-01

A heuristic diagram of the evolution of the standard genetic code is presented. It incorporates, in a way that resembles the energy levels of an atom, the physical notion of broken symmetry and it is consistent with original ideas by Crick on the origin and evolution of the code as well as with the chronological order of appearance of the amino acids along the evolution as inferred from work that mixtures known experimental results with theoretical speculations. Suggested by the diagram we propose a Hamilton quaternions based mathematical representation of the code as it stands now-a-days. The central object in the description is a codon function that assigns to each amino acid an integer quaternion in such a way that the observed code degeneration is preserved. We emphasize the advantages of a quaternionic representation of amino acids taking as an example the folding of proteins. With this aim we propose an algorithm to go from the quaternions sequence to the protein three dimensional structure which can be compared with the corresponding experimental one stored at the Protein Data Bank. In our criterion the mathematical representation of the genetic code in terms of quaternions merits to be taken into account because it describes not only most of the known properties of the genetic code but also opens new perspectives that are mainly derived from the close relationship between quaternions and rotations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Predictions of one-group interfacial area transport in TRACE

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

Worosz, T.; Talley, J. D.; Kim, S.

In current nuclear reactor system analysis codes utilizing the two-fluid model, flow regime dependent correlations are used to specify the interfacial area concentration (a i). This approach does not capture the continuous evolution of the interfacial structures, and thus, it can pose issues near the transition boundaries. Consequently, a pilot version of the system analysis code TRACE is being developed that employs the interfacial area transport equation (IATE). In this approach, dynamic estimation of a i is provided through mechanistic models for bubble coalescence and breakup. The implementation of the adiabatic, one-group IATE into TRACE is assessed against experimental datamore » from 50 air-water, two-phase flow conditions in pipes ranging in inner diameter from 2.54 to 20.32 cm for both vertical co-current upward and downward flows. Predictions of pressure, void fraction, bubble velocity, and a i data are made. TRACE employing the conventional flow regime-based approach is found to underestimate a i and can only predict linear trends since the calculation is governed by the pressure. Furthermore, trends opposite to that of the data are predicted for some conditions. In contrast, TRACE with the one-group IATE demonstrates a significant improvement in predicting the experimental data with an average disagreement of {+-} 13%. Additionally, TRACE with the one-group IATE is capable of predicting nonlinear axial development of a, by accounting for various bubble interaction mechanisms, such as coalescence and disintegration. (authors)« less

SNPmplexViewer--toward a cost-effective traceability system

PubMed Central

2011-01-01

Background Beef traceability has become mandatory in many regions of the world and is typically achieved through the use of unique numerical codes on ear tags and animal passports. DNA-based traceability uses the animal's own DNA code to identify it and the products derived from it. Using SNaPshot, a primer-extension-based method, a multiplex of 25 SNPs in a single reaction has been practiced for reducing the expense of genotyping a panel of SNPs useful for identity control. Findings To further decrease SNaPshot's cost, we introduced the Perl script SNPmplexViewer, which facilitates the analysis of trace files for reactions performed without the use of fluorescent size standards. SNPmplexViewer automatically aligns reference and target trace electropherograms, run with and without fluorescent size standards, respectively. SNPmplexViewer produces a modified target trace file containing a normalised trace in which the reference size standards are embedded. SNPmplexViewer also outputs aligned images of the two electropherograms together with a difference profile. Conclusions Modified trace files generated by SNPmplexViewer enable genotyping of SnaPshot reactions performed without fluorescent size standards, using common fragment-sizing software packages. SNPmplexViewer's normalised output may also improve the genotyping software's performance. Thus, SNPmplexViewer is a general free tool enabling the reduction of SNaPshot's cost as well as the fast viewing and comparing of trace electropherograms for fragment analysis. SNPmplexViewer is available at http://cowry.agri.huji.ac.il/cgi-bin/SNPmplexViewer.cgi. PMID:21600063

Introduction to the Natural Anticipator and the Artificial Anticipator

NASA Astrophysics Data System (ADS)

Dubois, Daniel M.

2010-11-01

This short communication deals with the introduction of the concept of anticipator, which is one who anticipates, in the framework of computing anticipatory systems. The definition of anticipation deals with the concept of program. Indeed, the word program, comes from "pro-gram" meaning "to write before" by anticipation, and means a plan for the programming of a mechanism, or a sequence of coded instructions that can be inserted into a mechanism, or a sequence of coded instructions, as genes or behavioural responses, that is part of an organism. Any natural or artificial programs are thus related to anticipatory rewriting systems, as shown in this paper. All the cells in the body, and the neurons in the brain, are programmed by the anticipatory genetic code, DNA, in a low-level language with four signs. The programs in computers are also computing anticipatory systems. It will be shown, at one hand, that the genetic code DNA is a natural anticipator. As demonstrated by Nobel laureate McClintock [8], genomes are programmed. The fundamental program deals with the DNA genetic code. The properties of the DNA consist in self-replication and self-modification. The self-replicating process leads to reproduction of the species, while the self-modifying process leads to new species or evolution and adaptation in existing ones. The genetic code DNA keeps its instructions in memory in the DNA coding molecule. The genetic code DNA is a rewriting system, from DNA coding to DNA template molecule. The DNA template molecule is a rewriting system to the Messenger RNA molecule. The information is not destroyed during the execution of the rewriting program. On the other hand, it will be demonstrated that Turing machine is an artificial anticipator. The Turing machine is a rewriting system. The head reads and writes, modifying the content of the tape. The information is destroyed during the execution of the program. This is an irreversible process. The input data are lost.

Accurate Ray-tracing of Realistic Neutron Star Atmospheres for Constraining Their Parameters

NASA Astrophysics Data System (ADS)

Vincent, Frederic H.; Bejger, Michał; Różańska, Agata; Straub, Odele; Paumard, Thibaut; Fortin, Morgane; Madej, Jerzy; Majczyna, Agnieszka; Gourgoulhon, Eric; Haensel, Paweł; Zdunik, Leszek; Beldycki, Bartosz

2018-03-01

Thermal-dominated X-ray spectra of neutron stars in quiescent, transient X-ray binaries and neutron stars that undergo thermonuclear bursts are sensitive to mass and radius. The mass–radius relation of neutron stars depends on the equation of state (EoS) that governs their interior. Constraining this relation accurately is therefore of fundamental importance to understand the nature of dense matter. In this context, we introduce a pipeline to calculate realistic model spectra of rotating neutron stars with hydrogen and helium atmospheres. An arbitrarily fast-rotating neutron star with a given EoS generates the spacetime in which the atmosphere emits radiation. We use the LORENE/NROTSTAR code to compute the spacetime numerically and the ATM24 code to solve the radiative transfer equations self-consistently. Emerging specific intensity spectra are then ray-traced through the neutron star’s spacetime from the atmosphere to a distant observer with the GYOTO code. Here, we present and test our fully relativistic numerical pipeline. To discuss and illustrate the importance of realistic atmosphere models, we compare our model spectra to simpler models like the commonly used isotropic color-corrected blackbody emission. We highlight the importance of considering realistic model-atmosphere spectra together with relativistic ray-tracing to obtain accurate predictions. We also insist upon the crucial impact of the star’s rotation on the observables. Finally, we close a controversy that has been ongoing in the literature in the recent years, regarding the validity of the ATM24 code.

Biosemiotics: a new understanding of life.

PubMed

Barbieri, Marcello

2008-07-01

Biosemiotics is the idea that life is based on semiosis, i.e., on signs and codes. This idea has been strongly suggested by the discovery of the genetic code, but so far it has made little impact in the scientific world and is largely regarded as a philosophy rather than a science. The main reason for this is that modern biology assumes that signs and meanings do not exist at the molecular level, and that the genetic code was not followed by any other organic code for almost four billion years, which implies that it was an utterly isolated exception in the history of life. These ideas have effectively ruled out the existence of semiosis in the organic world, and yet there are experimental facts against all of them. If we look at the evidence of life without the preconditions of the present paradigm, we discover that semiosis is there, in every single cell, and that it has been there since the very beginning. This is what biosemiotics is really about. It is not a philosophy. It is a new scientific paradigm that is rigorously based on experimental facts. Biosemiotics claims that the genetic code (1) is a real code and (2) has been the first of a long series of organic codes that have shaped the history of life on our planet. The reality of the genetic code and the existence of other organic codes imply that life is based on two fundamental processes--copying and coding--and this in turn implies that evolution took place by two distinct mechanisms, i.e., by natural selection (based on copying) and by natural conventions (based on coding). It also implies that the copying of genes works on individual molecules, whereas the coding of proteins operates on collections of molecules, which means that different mechanisms of evolution exist at different levels of organization. This review intends to underline the scientific nature of biosemiotics, and to this purpose, it aims to prove (1) that the cell is a real semiotic system, (2) that the genetic code is a real code, (3) that evolution took place by natural selection and by natural conventions, and (4) that it was natural conventions, i.e., organic codes, that gave origin to the great novelties of macroevolution. Biological semiosis, in other words, is a scientific reality because the codes of life are experimental realities. The time has come, therefore, to acknowledge this fact of life, even if that means abandoning the present theoretical framework in favor of a more general one where biology and semiotics finally come together and become biosemiotics.

Efficacy of a Web-based Intelligent Tutoring System for Communicating Genetic Risk of Breast Cancer: A Fuzzy-Trace Theory Approach

PubMed Central

Wolfe, Christopher R.; Reyna, Valerie F.; Widmer, Colin L.; Cedillos, Elizabeth M.; Fisher, Christopher R.; Brust-Renck, Priscila G.; Weil, Audrey M.

2014-01-01

Background Many healthy women consider genetic testing for breast cancer risk, yet BRCA testing issues are complex. Objective Determining whether an intelligent tutor, BRCA Gist, grounded in fuzzy-trace theory (FTT), increases gist comprehension and knowledge about genetic testing for breast cancer risk, improving decision-making. Design In two experiments, 410 healthy undergraduate women were randomly assigned to one of three groups: an online module using a web-based tutoring system (BRCA Gist) that uses artificial intelligence technology, a second group read highly similar content from the NCI web site, and a third completed an unrelated tutorial. Intervention BRCA Gist applied fuzzy trace theory and was designed to help participants develop gist comprehension of topics relevant to decisions about BRCA genetic testing, including how breast cancer spreads, inherited genetic mutations, and base rates. Measures We measured content knowledge, gist comprehension of decision-relevant information, interest in testing, and genetic risk and testing judgments. Results Control knowledge scores ranged from 54% to 56%, NCI improved significantly to 65% and 70%, and BRCA Gist improved significantly more to 75% and 77%, p<.0001. BRCA Gist scored higher on gist comprehension than NCI and control, p<.0001. Control genetic risk-assessment mean was 48% correct; BRCA Gist (61%), and NCI (56%) were significantly higher, p<.0001. BRCA Gist participants recommended less testing for women without risk factors (not good candidates), (24% and 19%) than controls (50%, both experiments) and NCI, (32%) Experiment 2, p<.0001. BRCA Gist testing interest was lower than controls, p<.0001. Limitations BRCA Gist has not been tested with older women from diverse groups. Conclusions Intelligent tutors, such as BRCA Gist, are scalable, cost effective ways of helping people understand complex issues, improving decision-making. PMID:24829276

Changes in mitochondrial genetic codes as phylogenetic characters: Two examples from the flatworms

PubMed Central

Telford, Maximilian J.; Herniou, Elisabeth A.; Russell, Robert B.; Littlewood, D. Timothy J.

2000-01-01

Shared molecular genetic characteristics other than DNA and protein sequences can provide excellent sources of phylogenetic information, particularly if they are complex and rare and are consequently unlikely to have arisen by chance convergence. We have used two such characters, arising from changes in mitochondrial genetic code, to define a clade within the Platyhelminthes (flatworms), the Rhabditophora. We have sampled 10 distinct classes within the Rhabditophora and find that all have the codon AAA coding for the amino acid Asn rather than the usual Lys and AUA for Ile rather than the usual Met. We find no evidence to support claims that the codon UAA codes for Tyr in the Platyhelminthes rather than the standard stop codon. The Rhabditophora are a very diverse group comprising the majority of the free-living turbellarian taxa and the parasitic Neodermata. In contrast, three other classes of turbellarian flatworm, the Acoela, Nemertodermatida, and Catenulida, have the standard invertebrate assignments for these codons and so are convincingly excluded from the rhabditophoran clade. We have developed a rapid computerized method for analyzing genetic codes and demonstrate the wide phylogenetic distribution of the standard invertebrate code as well as confirming already known metazoan deviations from it (ascidian, vertebrate, echinoderm/hemichordate). PMID:11027335

A Combinatorial Geometry Computer Description of the MEP-021A Generator Set

DTIC Science & Technology

1979-02-01

Generator Computer Description Gasoline Generator GIFT MEP-021A 20. ABSTRACT fCbntteu* an rararaa eta* ft namamwaay anal Identify by block number) This... GIFT code is also stored on magnetic tape for future vulnerability analysis. 00,] 󈧚*7,1473 EDITION OF • NOV 65 IS OBSOLETE UNCLASSIFIED SECURITY...the Geometric Information for Targets ( GIFT ) computer code. The GIFT code traces shotlines through a COM-GEOM description from any specified attack

Determining Hypocentral Parameters for Local Earthquakes in 1-D Using a Genetic Algorithm and Two-point ray tracing

NASA Astrophysics Data System (ADS)

Kim, W.; Hahm, I.; Ahn, S. J.; Lim, D. H.

2005-12-01

This paper introduces a powerful method for determining hypocentral parameters for local earthquakes in 1-D using a genetic algorithm (GA) and two-point ray tracing. Using existing algorithms to determine hypocentral parameters is difficult, because these parameters can vary based on initial velocity models. We developed a new method to solve this problem by applying a GA to an existing algorithm, HYPO-71 (Lee and Larh, 1975). The original HYPO-71 algorithm was modified by applying two-point ray tracing and a weighting factor with respect to the takeoff angle at the source to reduce errors from the ray path and hypocenter depth. Artificial data, without error, were generated by computer using two-point ray tracing in a true model, in which velocity structure and hypocentral parameters were known. The accuracy of the calculated results was easily determined by comparing calculated and actual values. We examined the accuracy of this method for several cases by changing the true and modeled layer numbers and thicknesses. The computational results show that this method determines nearly exact hypocentral parameters without depending on initial velocity models. Furthermore, accurate and nearly unique hypocentral parameters were obtained, although the number of modeled layers and thicknesses differed from those in the true model. Therefore, this method can be a useful tool for determining hypocentral parameters in regions where reliable local velocity values are unknown. This method also provides the basic a priori information for 3-D studies. KEY -WORDS: hypocentral parameters, genetic algorithm (GA), two-point ray tracing

Biosemiotics: a new understanding of life

NASA Astrophysics Data System (ADS)

Barbieri, Marcello

2008-07-01

Biosemiotics is the idea that life is based on semiosis, i.e., on signs and codes. This idea has been strongly suggested by the discovery of the genetic code, but so far it has made little impact in the scientific world and is largely regarded as a philosophy rather than a science. The main reason for this is that modern biology assumes that signs and meanings do not exist at the molecular level, and that the genetic code was not followed by any other organic code for almost four billion years, which implies that it was an utterly isolated exception in the history of life. These ideas have effectively ruled out the existence of semiosis in the organic world, and yet there are experimental facts against all of them. If we look at the evidence of life without the preconditions of the present paradigm, we discover that semiosis is there, in every single cell, and that it has been there since the very beginning. This is what biosemiotics is really about. It is not a philosophy. It is a new scientific paradigm that is rigorously based on experimental facts. Biosemiotics claims that the genetic code (1) is a real code and (2) has been the first of a long series of organic codes that have shaped the history of life on our planet. The reality of the genetic code and the existence of other organic codes imply that life is based on two fundamental processes—copying and coding—and this in turn implies that evolution took place by two distinct mechanisms, i.e., by natural selection (based on copying) and by natural conventions (based on coding). It also implies that the copying of genes works on individual molecules, whereas the coding of proteins operates on collections of molecules, which means that different mechanisms of evolution exist at different levels of organization. This review intends to underline the scientific nature of biosemiotics, and to this purpose, it aims to prove (1) that the cell is a real semiotic system, (2) that the genetic code is a real code, (3) that evolution took place by natural selection and by natural conventions, and (4) that it was natural conventions, i.e., organic codes, that gave origin to the great novelties of macroevolution. Biological semiosis, in other words, is a scientific reality because the codes of life are experimental realities. The time has come, therefore, to acknowledge this fact of life, even if that means abandoning the present theoretical framework in favor of a more general one where biology and semiotics finally come together and become biosemiotics.

File Compression and Expansion of the Genetic Code by the use of the Yin/Yang Directions to find its Sphered Cube

PubMed Central

Castro-Chavez, Fernando

2014-01-01

Objective The objective of this article is to demonstrate that the genetic code can be studied and represented in a 3-D Sphered Cube for bioinformatics and for education by using the graphical help of the ancient “Book of Changes” or I Ching for the comparison, pair by pair, of the three basic characteristics of nucleotides: H-bonds, molecular structure, and their tautomerism. Methods The source of natural biodiversity is the high plasticity of the genetic code, analyzable with a reverse engineering of its 2-D and 3-D representations (here illustrated), but also through the classical 64-hexagrams of the ancient I Ching, as if they were the 64-codons or words of the genetic code. Results In this article, the four elements of the Yin/Yang were found by correlating the 3×2=6 sets of Cartesian comparisons of the mentioned properties of nucleic acids, to the directionality of their resulting blocks of codons grouped according to their resulting amino acids and/or functions, integrating a 384-codon Sphered Cube whose function is illustrated by comparing six brain peptides and a promoter of osteoblasts from Humans versus Neanderthal, as well as to Negadi’s work on the importance of the number 384 within the genetic code. Conclusions Starting with the codon/anticodon correlation of Nirenberg, published in full here for the first time, and by studying the genetic code and its 3-D display, the buffers of reiteration within codons codifying for the same amino acid, displayed the two long (binary number one) and older Yin/Yang arrows that travel in opposite directions, mimicking the parental DNA strands, while annealing to the two younger and broken (binary number zero) Yin/Yang arrows, mimicking the new DNA strands; the graphic analysis of the of the genetic code and its plasticity was helpful to compare compatible sequences (human compatible to human versus neanderthal compatible to neanderthal), while further exploring the wondrous biodiversity of nature for educational purposes. PMID:25340175

3D Laser Imprint Using a Smoother Ray-Traced Power Deposition Method

NASA Astrophysics Data System (ADS)

Schmitt, Andrew J.

2017-10-01

Imprinting of laser nonuniformities in directly-driven icf targets is a challenging problem to accurately simulate with large radiation-hydro codes. One of the most challenging aspects is the proper construction of the complex and rapidly changing laser interference structure driving the imprint using the reduced laser propagation models (usually ray-tracing) found in these codes. We have upgraded the modelling capability in our massively-parallel fastrad3d code by adding a more realistic EM-wave interference structure. This interference model adds an axial laser speckle to the previous transverse-only laser structure, and can be impressed on our improved smoothed 3D raytrace package. This latter package, which connects rays to form bundles and performs power deposition calculations on the bundles, is intended to decrease ray-trace noise (which can mask or add to imprint) while using fewer rays. We apply this improved model to 3D simulations of recent imprint experiments performed on the Omega-EP laser and the Nike laser that examined the reduction of imprinting due to very thin high-Z target coatings. We report on the conditions in which this new model makes a significant impact on the development of laser imprint. Supported by US DoE/NNSA.

Energy-Constrained Recharge, Assimilation, and Fractional Crystallization (EC-RAχFC): A Visual Basic computer code for calculating trace element and isotope variations of open-system magmatic systems

NASA Astrophysics Data System (ADS)

Bohrson, Wendy A.; Spera, Frank J.

2007-11-01

Volcanic and plutonic rocks provide abundant evidence for complex processes that occur in magma storage and transport systems. The fingerprint of these processes, which include fractional crystallization, assimilation, and magma recharge, is captured in petrologic and geochemical characteristics of suites of cogenetic rocks. Quantitatively evaluating the relative contributions of each process requires integration of mass, species, and energy constraints, applied in a self-consistent way. The energy-constrained model Energy-Constrained Recharge, Assimilation, and Fractional Crystallization (EC-RaχFC) tracks the trace element and isotopic evolution of a magmatic system (melt + solids) undergoing simultaneous fractional crystallization, recharge, and assimilation. Mass, thermal, and compositional (trace element and isotope) output is provided for melt in the magma body, cumulates, enclaves, and anatectic (i.e., country rock) melt. Theory of the EC computational method has been presented by Spera and Bohrson (2001, 2002, 2004), and applications to natural systems have been elucidated by Bohrson and Spera (2001, 2003) and Fowler et al. (2004). The purpose of this contribution is to make the final version of the EC-RAχFC computer code available and to provide instructions for code implementation, description of input and output parameters, and estimates of typical values for some input parameters. A brief discussion highlights measures by which the user may evaluate the quality of the output and also provides some guidelines for implementing nonlinear productivity functions. The EC-RAχFC computer code is written in Visual Basic, the programming language of Excel. The code therefore launches in Excel and is compatible with both PC and MAC platforms. The code is available on the authors' Web sites http://magma.geol.ucsb.edu/and http://www.geology.cwu.edu/ecrafc) as well as in the auxiliary material.

Genetic Code Expansion of Mammalian Cells with Unnatural Amino Acids.

PubMed

Brown, Kalyn A; Deiters, Alexander

2015-09-01

The expansion of the genetic code of mammalian cells enables the incorporation of unnatural amino acids into proteins. This is achieved by adding components to the protein biosynthetic machinery, specifically an engineered aminoacyl-tRNA synthetase/tRNA pair. The unnatural amino acids are chemically synthesized and supplemented to the growth medium. Using this methodology, fundamental new chemistries can be added to the functional repertoire of the genetic code of mammalian cells. This protocol outlines the steps necessary to incorporate a photocaged lysine into proteins and showcases its application in the optical triggering of protein translocation to the nucleus. Copyright © 2015 John Wiley & Sons, Inc.

Genetic Model Fitting in IQ, Assortative Mating & Components of IQ Variance.

ERIC Educational Resources Information Center

Capron, Christiane; Vetta, Adrian R.; Vetta, Atam

1998-01-01

The biometrical school of scientists who fit models to IQ data traces their intellectual ancestry to R. Fisher (1918), but their genetic models have no predictive value. Fisher himself was critical of the concept of heritability, because assortative mating, such as for IQ, introduces complexities into the study of a genetic trait. (SLD)

Possibilities for the evolution of the genetic code from a preceding form

NASA Technical Reports Server (NTRS)

Jukes, T. H.

1973-01-01

Analysis of the interaction between mRNA codons and tRNA anticodons suggests a model for the evolution of the genetic code. Modification of the nucleic acid following the anticodon is at present essential in both eukaryotes and prokaryotes to ensure fidelity of translation of codons starting with A, and the amino acids which could be coded for before the evolution of the modifying enzymes can be deduced.

"Counseling" in Ophthalmology.

ERIC Educational Resources Information Center

Francois, J.

1976-01-01

The need to counsel patients with genetic ophthalmological problems is stressed in the article. Assessment of autosomal dominance or autosomal recessitivity in an individual is explained and sex-linked heredity is traced. Practical examples of genetic abnormalities, such as pigmentary retinopathy and chorodineremia, are discussed. (PHR)

I-Ching, dyadic groups of binary numbers and the geno-logic coding in living bodies.

PubMed

Hu, Zhengbing; Petoukhov, Sergey V; Petukhova, Elena S

2017-12-01

The ancient Chinese book I-Ching was written a few thousand years ago. It introduces the system of symbols Yin and Yang (equivalents of 0 and 1). It had a powerful impact on culture, medicine and science of ancient China and several other countries. From the modern standpoint, I-Ching declares the importance of dyadic groups of binary numbers for the Nature. The system of I-Ching is represented by the tables with dyadic groups of 4 bigrams, 8 trigrams and 64 hexagrams, which were declared as fundamental archetypes of the Nature. The ancient Chinese did not know about the genetic code of protein sequences of amino acids but this code is organized in accordance with the I-Ching: in particularly, the genetic code is constructed on DNA molecules using 4 nitrogenous bases, 16 doublets, and 64 triplets. The article also describes the usage of dyadic groups as a foundation of the bio-mathematical doctrine of the geno-logic code, which exists in parallel with the known genetic code of amino acids but serves for a different goal: to code the inherited algorithmic processes using the logical holography and the spectral logic of systems of genetic Boolean functions. Some relations of this doctrine with the I-Ching are discussed. In addition, the ratios of musical harmony that can be revealed in the parameters of DNA structure are also represented in the I-Ching book. Copyright © 2017 Elsevier Ltd. All rights reserved.

On the possible origin and evolution of the genetic code

NASA Technical Reports Server (NTRS)

Jukes, T. H.

1974-01-01

The genetic code is examined for indications of possible preceding codes that existed during early evolution. Eight of the 20 amino acids are coded by 'quartets' of codons with fourfold degeneracy, and 16 such quartets can exist, so that an earlier code could have provided for 15 or 16 amino acids, rather than 20. If twofold degeneracy is postulated for the first position of the codon, there could have been ten amino acids in the code. It is speculated that these may have been phenylalanine, valine, proline, alanine, histidine, glutamine, glutanic acid, aspartic acid, cysteine and glycine. There is a notable deficiency of arginine in proteins, despite the fact that it has six codons. Simultaneously, there is more lysine in proteins than would be expected from its two codons, if the four bases in mRNA are equiprobable and are arranged randomly. It is speculated that arginine is an 'intruder' into the genetic code, and that it may have displayed another amino acid such as ornithine, or may even have displayed lysine from some of its previous codon assignments. As a result, natural selection has favored lysine against the fact that it has only two codons.

A Combinatorial Geometry Computer Description of the M9 ACE (Armored Combat Earthmover) Vehicle

DTIC Science & Technology

1984-12-01

program requires as input the M9 target descriptions as processed by the Geometric Information for Targets ( GIFT ) ’ computer code. The first step is...model of the target. This COM-GEOM target description is used as input to the Geometric Information For Targets ( GIFT ) computer code. Among other...things, the GIFT code traces shotlines through a COM-GEOM description from any specified aspect, listing pertinent information about each component hit

FLiT: a field line trace code for magnetic confinement devices

NASA Astrophysics Data System (ADS)

Innocente, P.; Lorenzini, R.; Terranova, D.; Zanca, P.

2017-04-01

This paper presents a field line tracing code (FLiT) developed to study particle and energy transport as well as other phenomena related to magnetic topology in reversed-field pinch (RFP) and tokamak experiments. The code computes magnetic field lines in toroidal geometry using curvilinear coordinates (r, ϑ, ϕ) and calculates the intersections of these field lines with specified planes. The code also computes the magnetic and thermal diffusivity due to stochastic magnetic field in the collisionless limit. Compared to Hamiltonian codes, there are no constraints on the magnetic field functional formulation, which allows the integration of whichever magnetic field is required. The code uses the magnetic field computed by solving the zeroth-order axisymmetric equilibrium and the Newcomb equation for the first-order helical perturbation matching the edge magnetic field measurements in toroidal geometry. Two algorithms are developed to integrate the field lines: one is a dedicated implementation of a first-order semi-implicit volume-preserving integration method, and the other is based on the Adams-Moulton predictor-corrector method. As expected, the volume-preserving algorithm is accurate in conserving divergence, but slow because the low integration order requires small amplitude steps. The second algorithm proves to be quite fast and it is able to integrate the field lines in many partially and fully stochastic configurations accurately. The code has already been used to study the core and edge magnetic topology of the RFX-mod device in both the reversed-field pinch and tokamak magnetic configurations.

Ordering Traces Logically to Identify Lateness in Message Passing Programs

DOE PAGES

Isaacs, Katherine E.; Gamblin, Todd; Bhatele, Abhinav; ...

2015-03-30

Event traces are valuable for understanding the behavior of parallel programs. However, automatically analyzing a large parallel trace is difficult, especially without a specific objective. We aid this endeavor by extracting a trace's logical structure, an ordering of trace events derived from happened-before relationships, while taking into account developer intent. Using this structure, we can calculate an operation's delay relative to its peers on other processes. The logical structure also serves as a platform for comparing and clustering processes as well as highlighting communication patterns in a trace visualization. We present an algorithm for determining this idealized logical structure frommore » traces of message passing programs, and we develop metrics to quantify delays and differences among processes. We implement our techniques in Ravel, a parallel trace visualization tool that displays both logical and physical timelines. Rather than showing the duration of each operation, we display where delays begin and end, and how they propagate. As a result, we apply our approach to the traces of several message passing applications, demonstrating the accuracy of our extracted structure and its utility in analyzing these codes.« less

Students' Views and Attitudes Towards the Communication Code Used in Press Articles about Science

ERIC Educational Resources Information Center

Halkia, Krystallia; Mantzouridis, Dimitris

2005-01-01

The present research was designed to investigate the reaction of secondary school students to the communication code that the press uses in science articles: it attempts to trace which communication techniques can be of potential use in science education. The sample of the research consists of 351 secondary school students. The research instrument…

Sticks and Stones: Why First Amendment Absolutism Fails When Applied to Campus Harassment Codes.

ERIC Educational Resources Information Center

Lumsden, Linda

This paper analyzes how absolutist arguments against campus harassment codes violate the spirit of the first amendment, examining in particular the United States Supreme Court ruling in "RAV v. St. Paul." The paper begins by tracing the current development of first amendment doctrine, analyzing its inadequacy in the campus hate speech…

Ancient DNA sequence revealed by error-correcting codes.

PubMed

Brandão, Marcelo M; Spoladore, Larissa; Faria, Luzinete C B; Rocha, Andréa S L; Silva-Filho, Marcio C; Palazzo, Reginaldo

2015-07-10

A previously described DNA sequence generator algorithm (DNA-SGA) using error-correcting codes has been employed as a computational tool to address the evolutionary pathway of the genetic code. The code-generated sequence alignment demonstrated that a residue mutation revealed by the code can be found in the same position in sequences of distantly related taxa. Furthermore, the code-generated sequences do not promote amino acid changes in the deviant genomes through codon reassignment. A Bayesian evolutionary analysis of both code-generated and homologous sequences of the Arabidopsis thaliana malate dehydrogenase gene indicates an approximately 1 MYA divergence time from the MDH code-generated sequence node to its paralogous sequences. The DNA-SGA helps to determine the plesiomorphic state of DNA sequences because a single nucleotide alteration often occurs in distantly related taxa and can be found in the alternative codon patterns of noncanonical genetic codes. As a consequence, the algorithm may reveal an earlier stage of the evolution of the standard code.

Ancient DNA sequence revealed by error-correcting codes

PubMed Central

Brandão, Marcelo M.; Spoladore, Larissa; Faria, Luzinete C. B.; Rocha, Andréa S. L.; Silva-Filho, Marcio C.; Palazzo, Reginaldo

2015-01-01

A previously described DNA sequence generator algorithm (DNA-SGA) using error-correcting codes has been employed as a computational tool to address the evolutionary pathway of the genetic code. The code-generated sequence alignment demonstrated that a residue mutation revealed by the code can be found in the same position in sequences of distantly related taxa. Furthermore, the code-generated sequences do not promote amino acid changes in the deviant genomes through codon reassignment. A Bayesian evolutionary analysis of both code-generated and homologous sequences of the Arabidopsis thaliana malate dehydrogenase gene indicates an approximately 1 MYA divergence time from the MDH code-generated sequence node to its paralogous sequences. The DNA-SGA helps to determine the plesiomorphic state of DNA sequences because a single nucleotide alteration often occurs in distantly related taxa and can be found in the alternative codon patterns of noncanonical genetic codes. As a consequence, the algorithm may reveal an earlier stage of the evolution of the standard code. PMID:26159228

Traceability of biotech-derived animals: application of DNA technology.

PubMed

Loftus, R

2005-04-01

Traceability is increasingly becoming standard across the agri-food industry, largely driven by recent food crises and the consequent demands for transparency within the food chain. This is leading to the development of a range of traceability concepts and technologies adapted to different industry needs. Experience with genetically modified plants has shown that traceability can play a role in increasing public confidence in biotechnology, and might similarly help allay concerns relating to the development of animal biotechnology. Traceability also forms an essential component of any risk management strategy and is a key requirement for post-marketing surveillance. Given the diversity of traceability concepts and technologies available, consideration needs to be given to the scope and precision of traceability systems for animal biotechnology. Experience to date has shown that conventional tagging and labelling systems can incorporate levels of error and may not have sufficient precision for biotech-derived animals. Deoxyribonucleic acid (DNA) technology can overcome these difficulties by tracing animals and animal by-products through their DNA code rather than an associated label. This offers the possibility of tracing some by-products of animal biotechnology through the supply chain back to source animals, offering unprecedented levels of traceability. Developments in both DNA sampling and analysis technology are making large-scale applications of DNA traceability increasingly cost effective and feasible, and are likely to lead to a broader uptake of DNA traceability concepts.

Genetic Lineage Tracing of Non-Myocyte Population by Dual Recombinases.

PubMed

Li, Yan; He, Lingjuan; Huang, Xiuzhen; Issa Bhaloo, Shirin; Zhao, Huan; Zhang, Shaohua; Pu, Wenjuan; Tian, Xueying; Li, Yi; Liu, Qiaozhen; Yu, Wei; Zhang, Libo; Liu, Xiuxiu; Liu, Kuo; Tang, Juan; Zhang, Hui; Cai, Dongqing; Adams, Ralf H; Xu, Qingbo; Lui, Kathy O; Zhou, Bin

2018-04-26

Background -Whether the adult mammalian heart harbors cardiac stem cells (CSCs) for regeneration of cardiomyocytes is an important yet contentious topic in the field of cardiovascular regeneration. The putative myocyte stem cell populations recognized without specific cell markers such as the cardiosphere-derived cells or with markers such as Sca1 + , Bmi1 + , Isl1 + or Abcg2 + CSCs have been reported. Moreover, it remains unclear whether putative CSCs with unknown or unidentified markers exist and give rise to de novo cardiomyocytes in the adult heart. Methods -To address this question without relying on a particular stem cell marker, we developed a new genetic lineage tracing system to label all non-myocyte populations that contain putative CSCs. Using dual lineage tracing system, we assessed if non-myocytes generated any new myocytes during embryonic development, adult homeostasis and after myocardial infarction. Skeletal muscle was also examined after injury for internal control of new myocytes generation from non-myocytes. Results -By this stem cell marker-free and dual recombinases-mediated cell tracking approach, our fate mapping data show that new myocytes arise from non-myocytes in the embryonic heart, but not in the adult heart during homeostasis or after myocardial infarction. As positive control, our lineage tracing system detected new myocytes derived from non-myocytes in the skeletal muscle after injury. Conclusions -This study provides in vivo genetic evidence for non-myocyte to myocyte conversion in embryonic but not adult heart, arguing again the myogenic potential of putative stem cell populations for cardiac regeneration in the adult stage. This study also provides a new genetic strategy to identify endogenous stem cells, if any, in other organ systems for tissue repair and regeneration.

Guidelines for Coding and Entering Ground-Water Data into the Ground-Water Site Inventory Data Base, Version 4.6, U.S. Geological Survey, Washington Water Science Center

DTIC Science & Technology

2006-01-01

collected, code both. Code Type of Analysis Code Type of Analysis A Physical properties I Common ions/trace elements B Common ions J Sanitary analysis and...1) A ground-water site is coded as if it is a single point, not a geographic area or property . (2) Latitude and longitude should be determined at a...terrace from an adjacent upland on one side, and a lowland coast or valley on the other. Due to the effects of erosion, the terrace surface may not be as

Summary of evidence for an anticodonic basis for the origin of the genetic code

NASA Technical Reports Server (NTRS)

Lacey, J. C., Jr.; Mullins, D. W., Jr.

1981-01-01

This article summarizes data supporting the hypothesis that the genetic code origin was based on relationships (probably affinities) between amino acids and their anticodon nucleotides. Selective activation seems to follow from selective affinity and consequently, incorporation of amino acids into peptides can also be selective. It is suggested that these selectivities in affinity and activation, coupled with the base pairing specificities, allowed the origin of the code and the process of translation.

SU-D-206-02: Evaluation of Partial Storage of the System Matrix for Cone Beam Computed Tomography Using a GPU Platform

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

Matenine, D; Cote, G; Mascolo-Fortin, J

2016-06-15

Purpose: Iterative reconstruction algorithms in computed tomography (CT) require a fast method for computing the intersections between the photons’ trajectories and the object, also called ray-tracing or system matrix computation. This work evaluates different ways to store the system matrix, aiming to reconstruct dense image grids in reasonable time. Methods: We propose an optimized implementation of the Siddon’s algorithm using graphics processing units (GPUs) with a novel data storage scheme. The algorithm computes a part of the system matrix on demand, typically, for one projection angle. The proposed method was enhanced with accelerating options: storage of larger subsets of themore » system matrix, systematic reuse of data via geometric symmetries, an arithmetic-rich parallel code and code configuration via machine learning. It was tested on geometries mimicking a cone beam CT acquisition of a human head. To realistically assess the execution time, the ray-tracing routines were integrated into a regularized Poisson-based reconstruction algorithm. The proposed scheme was also compared to a different approach, where the system matrix is fully pre-computed and loaded at reconstruction time. Results: Fast ray-tracing of realistic acquisition geometries, which often lack spatial symmetry properties, was enabled via the proposed method. Ray-tracing interleaved with projection and backprojection operations required significant additional time. In most cases, ray-tracing was shown to use about 66 % of the total reconstruction time. In absolute terms, tracing times varied from 3.6 s to 7.5 min, depending on the problem size. The presence of geometrical symmetries allowed for non-negligible ray-tracing and reconstruction time reduction. Arithmetic-rich parallel code and machine learning permitted a modest reconstruction time reduction, in the order of 1 %. Conclusion: Partial system matrix storage permitted the reconstruction of higher 3D image grid sizes and larger projection datasets at the cost of additional time, when compared to the fully pre-computed approach. This work was supported in part by the Fonds de recherche du Quebec - Nature et technologies (FRQ-NT). The authors acknowledge partial support by the CREATE Medical Physics Research Training Network grant of the Natural Sciences and Engineering Research Council of Canada (Grant No. 432290).« less

Ray-tracing critical-angle transmission gratings for the X-ray Surveyor and Explorer-size missions

NASA Astrophysics Data System (ADS)

Günther, Hans M.; Bautz, Marshall W.; Heilmann, Ralf K.; Huenemoerder, David P.; Marshall, Herman L.; Nowak, Michael A.; Schulz, Norbert S.

2016-07-01

We study a critical angle transmission (CAT) grating spectrograph that delivers a spectral resolution significantly above any X-ray spectrograph ever own. This new technology will allow us to resolve kinematic components in absorption and emission lines of galactic and extragalactic matter down to unprecedented dispersion levels. We perform ray-trace simulations to characterize the performance of the spectrograph in the context of an X-ray Surveyor or Arcus like layout (two mission concepts currently under study). Our newly developed ray-trace code is a tool suite to simulate the performance of X-ray observatories. The simulator code is written in Python, because the use of a high-level scripting language allows modifications of the simulated instrument design in very few lines of code. This is especially important in the early phase of mission development, when the performances of different configurations are contrasted. To reduce the run-time and allow for simulations of a few million photons in a few minutes on a desktop computer, the simulator code uses tabulated input (from theoretical models or laboratory measurements of samples) for grating efficiencies and mirror reflectivities. We find that the grating facet alignment tolerances to maintain at least 90% of resolving power that the spectrometer has with perfect alignment are (i) translation parallel to the optical axis below 0.5 mm, (ii) rotation around the optical axis or the groove direction below a few arcminutes, and (iii) constancy of the grating period to 1:105. Translations along and rotations around the remaining axes can be significantly larger than this without impacting the performance.

Nuclear fuel management optimization using genetic algorithms

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

DeChaine, M.D.; Feltus, M.A.

1995-07-01

The code independent genetic algorithm reactor optimization (CIGARO) system has been developed to optimize nuclear reactor loading patterns. It uses genetic algorithms (GAs) and a code-independent interface, so any reactor physics code (e.g., CASMO-3/SIMULATE-3) can be used to evaluate the loading patterns. The system is compared to other GA-based loading pattern optimizers. Tests were carried out to maximize the beginning of cycle k{sub eff} for a pressurized water reactor core loading with a penalty function to limit power peaking. The CIGARO system performed well, increasing the k{sub eff} after lowering the peak power. Tests of a prototype parallel evaluation methodmore » showed the potential for a significant speedup.« less

Chemical studies of H chondrites. I - Mobile trace elements and gas retention ages

NASA Technical Reports Server (NTRS)

Lingner, David W.; Huston, Ted J.; Hutson, Melinda; Lipschutz, Michael E.

1987-01-01

Trends for 16 trace elements (Ag, As, Au, Bi, Cd, Co, Cs, Ga, In, K, Rb, Sb, Se, Te, Tl, and Zn), chosen to span a broad geochemical and thermal response range, in 44 H4-6 chondrites, differ widely from those in L4-6 chondrites. In particular, H chondrites classified as heavily shocked petrologically do not necessarily exhibit Ar-40 loss and vice versa. The clear-cut causal relationship between siderophile and mobile element loss with increasing late shock seen in L chondrites is not generally evident in the H group. H chondrite parent material experienced an early high temperature genetic episode that mobilized a substantial proportion of these trace elements so that later thermal episodes resulted in more subtle, collateral fractionations. Mildly shocked L chondrites escaped this early high temperature event, indicating that the two most numerous meteorite groups differ fundamentally in genetic history.

Clinical application of antenatal genetic diagnosis of osteogenesis imperfecta type IV.

PubMed

Yuan, Jing; Li, Song; Xu, YeYe; Cong, Lin

2015-04-02

Clinical analysis and genetic testing of a family with osteogenesis imperfecta type IV were conducted, aiming to discuss antenatal genetic diagnosis of osteogenesis imperfecta type IV. Preliminary genotyping was performed based on clinical characteristics of the family members and then high-throughput sequencing was applied to rapidly and accurately detect the changes in candidate genes. Genetic testing of the III5 fetus and other family members revealed missense mutation in c.2746G>A, pGly916Arg in COL1A2 gene coding region and missense and synonymous mutation in COL1A1 gene coding region. Application of antenatal genetic diagnosis provides fast and accurate genetic counseling and eugenics suggestions for patients with osteogenesis imperfecta type IV and their families.

Generating Code Review Documentation for Auto-Generated Mission-Critical Software

NASA Technical Reports Server (NTRS)

Denney, Ewen; Fischer, Bernd

2009-01-01

Model-based design and automated code generation are increasingly used at NASA to produce actual flight code, particularly in the Guidance, Navigation, and Control domain. However, since code generators are typically not qualified, there is no guarantee that their output is correct, and consequently auto-generated code still needs to be fully tested and certified. We have thus developed AUTOCERT, a generator-independent plug-in that supports the certification of auto-generated code. AUTOCERT takes a set of mission safety requirements, and formally verifies that the autogenerated code satisfies these requirements. It generates a natural language report that explains why and how the code complies with the specified requirements. The report is hyper-linked to both the program and the verification conditions and thus provides a high-level structured argument containing tracing information for use in code reviews.

Prevention of congenital abnormalities by periconceptional multivitamin supplementation.

PubMed Central

Czeizel, A E

1993-01-01

OBJECTIVE--To study the effect of periconceptional multivitamin supplementation on neural tube defects and other congenital abnormality entities. DESIGN--Randomised controlled trial of supplementation with multivitamins and trace elements. SETTING--Hungarian family planning programme. SUBJECTS--4156 pregnancies with known outcome and 3713 infants evaluated in the eighth month of life. INTERVENTIONS--A single tablet of a multivitamin including 0.8 mg of folic acid or trace elements supplement daily for at least one month before conception and at least two months after conception. MAIN OUTCOME MEASURES--Number of major and mild congenital abnormalities. RESULTS--The rate of all major congenital abnormalities was significantly lower in the group given vitamins than in the group given trace elements and this difference cannot be explained totally by the significant reduction of neural tube defects. The rate of major congenital abnormalities other than neural tube defects and genetic syndromes was 9.0/1000 in pregnancies with known outcome in the vitamin group and 16.6/1000 in the trace element group; relative risk 1.85 (95% confidence interval 1.02 to 3.38); difference, 7.6/1000. The rate of all major congenital abnormalities other than neural tube defects and genetic syndromes diagnosed up to the eighth month of life was 14.7/1000 informative pregnancies in the vitamin group and 28.3/1000 in the trace element group; relative risk 1.95 (1.23 to 3.09); difference, 13.6/1000. The rate of some congenital abnormalities was lower in the vitamin group than in the trace element group but the differences for each group of abnormalities were not significant. CONCLUSIONS--Periconceptional multivitamin supplementation can reduce not only the rate of neural tube defects but also the rate of other major non-genetic syndromatic congenital abnormalities. Further studies are needed to differentiate the chance effect and vitamin dependent effect. PMID:8324432

Neutron transport analysis for nuclear reactor design

DOEpatents

Vujic, Jasmina L.

1993-01-01

Replacing regular mesh-dependent ray tracing modules in a collision/transfer probability (CTP) code with a ray tracing module based upon combinatorial geometry of a modified geometrical module (GMC) provides a general geometry transfer theory code in two dimensions (2D) for analyzing nuclear reactor design and control. The primary modification of the GMC module involves generation of a fixed inner frame and a rotating outer frame, where the inner frame contains all reactor regions of interest, e.g., part of a reactor assembly, an assembly, or several assemblies, and the outer frame, with a set of parallel equidistant rays (lines) attached to it, rotates around the inner frame. The modified GMC module allows for determining for each parallel ray (line), the intersections with zone boundaries, the path length between the intersections, the total number of zones on a track, the zone and medium numbers, and the intersections with the outer surface, which parameters may be used in the CTP code to calculate collision/transfer probability and cross-section values.

Neutron transport analysis for nuclear reactor design

DOEpatents

Vujic, J.L.

1993-11-30

Replacing regular mesh-dependent ray tracing modules in a collision/transfer probability (CTP) code with a ray tracing module based upon combinatorial geometry of a modified geometrical module (GMC) provides a general geometry transfer theory code in two dimensions (2D) for analyzing nuclear reactor design and control. The primary modification of the GMC module involves generation of a fixed inner frame and a rotating outer frame, where the inner frame contains all reactor regions of interest, e.g., part of a reactor assembly, an assembly, or several assemblies, and the outer frame, with a set of parallel equidistant rays (lines) attached to it, rotates around the inner frame. The modified GMC module allows for determining for each parallel ray (line), the intersections with zone boundaries, the path length between the intersections, the total number of zones on a track, the zone and medium numbers, and the intersections with the outer surface, which parameters may be used in the CTP code to calculate collision/transfer probability and cross-section values. 28 figures.

Identification of small non-coding RNA classes expressed in swine whole blood during HP-PRRSV infection

USDA-ARS?s Scientific Manuscript database

It has been established that reduced susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) has a genetic component. This genetic component may take the form of small non-coding RNAs (sncRNA), which are molecules that function as regulators of gene expression. Various sncRNAs ...

An automatic scaling method for obtaining the trace and parameters from oblique ionogram based on hybrid genetic algorithm

NASA Astrophysics Data System (ADS)

Song, Huan; Hu, Yaogai; Jiang, Chunhua; Zhou, Chen; Zhao, Zhengyu; Zou, Xianjian

2016-12-01

Scaling oblique ionogram plays an important role in obtaining ionospheric structure at the midpoint of oblique sounding path. The paper proposed an automatic scaling method to extract the trace and parameters of oblique ionogram based on hybrid genetic algorithm (HGA). The extracted 10 parameters come from F2 layer and Es layer, such as maximum observation frequency, critical frequency, and virtual height. The method adopts quasi-parabolic (QP) model to describe F2 layer's electron density profile that is used to synthesize trace. And it utilizes secant theorem, Martyn's equivalent path theorem, image processing technology, and echoes' characteristics to determine seven parameters' best fit values, and three parameter's initial values in QP model to set up their searching spaces which are the needed input data of HGA. Then HGA searches the three parameters' best fit values from their searching spaces based on the fitness between the synthesized trace and the real trace. In order to verify the performance of the method, 240 oblique ionograms are scaled and their results are compared with manual scaling results and the inversion results of the corresponding vertical ionograms. The comparison results show that the scaling results are accurate or at least adequate 60-90% of the time.

CRISPR-Barcoding for Intratumor Genetic Heterogeneity Modeling and Functional Analysis of Oncogenic Driver Mutations.

PubMed

Guernet, Alexis; Mungamuri, Sathish Kumar; Cartier, Dorthe; Sachidanandam, Ravi; Jayaprakash, Anitha; Adriouch, Sahil; Vezain, Myriam; Charbonnier, Françoise; Rohkin, Guy; Coutant, Sophie; Yao, Shen; Ainani, Hassan; Alexandre, David; Tournier, Isabelle; Boyer, Olivier; Aaronson, Stuart A; Anouar, Youssef; Grumolato, Luca

2016-08-04

Intratumor genetic heterogeneity underlies the ability of tumors to evolve and adapt to different environmental conditions. Using CRISPR/Cas9 technology and specific DNA barcodes, we devised a strategy to recapitulate and trace the emergence of subpopulations of cancer cells containing a mutation of interest. We used this approach to model different mechanisms of lung cancer cell resistance to EGFR inhibitors and to assess effects of combined drug therapies. By overcoming intrinsic limitations of current approaches, CRISPR-barcoding also enables investigation of most types of genetic modifications, including repair of oncogenic driver mutations. Finally, we used highly complex barcodes inserted at a specific genome location as a means of simultaneously tracing the fates of many thousands of genetically labeled cancer cells. CRISPR-barcoding is a straightforward and highly flexible method that should greatly facilitate the functional investigation of specific mutations, in a context that closely mimics the complexity of cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Introduction to the Security Engineering Risk Analysis (SERA) Framework

DTIC Science & Technology

2014-11-01

military aircraft has increased from 8% to 80%. At the same time, the size of software in military aircraft has grown from 1,000 lines of code in the F...4A to 1.7 million lines of code in the F-22. This growth trend is expected to con- tinue over time [NASA 2009]. As software exerts more control of...their root causes can be traced to the software’s requirements, architecture, design, or code . Studies have shown that the cost of addressing a software

[Direct genetic manipulation and criminal code in Venezuela: absolute criminal law void?].

PubMed

Cermeño Zambrano, Fernando G De J

2002-01-01

The judicial regulation of genetic biotechnology applied to the human genome is of big relevance currently in Venezuela due to the drafting of an innovative bioethical law in the country's parliament. This article will highlight the constitutional normative of Venezuela's 1999 Constitution regarding this subject, as it establishes the framework from which this matter will be legally regulated. The approach this article makes towards the genetic biotechnology applied to the human genome is made taking into account the Venezuelan penal law and by highlighting the violent genetic manipulations that have criminal relevance. The genetic biotechnology applied to the human genome has another important relevance as a consequence of the reformulation of the Venezuelan Penal Code discussed by the country's National Assembly. Therefore, a concise study of the country's penal code will be made in this article to better understand what judicial-penal properties have been protected by the Venezuelan penal legislation. This last step will enable us to identify the penal tools Venezuela counts on to face direct genetic manipulations. We will equally indicate the existing punitive loophole and that should be covered by the penal legislator. In conclusion, this essay concerns criminal policy, referred to the direct genetic manipulations on the human genome that haven't been typified in Venezuelan law, thus discovering a genetic biotechnology paradise.

A FORTRAN code for the calculation of probe volume geometry changes in a laser anemometry system caused by window refraction

NASA Technical Reports Server (NTRS)

Owen, Albert K.

1987-01-01

A computer code was written which utilizes ray tracing techniques to predict the changes in position and geometry of a laser Doppler velocimeter probe volume resulting from refraction effects. The code predicts the position change, changes in beam crossing angle, and the amount of uncrossing that occur when the beams traverse a region with a changed index of refraction, such as a glass window. The code calculates the changes for flat plate, cylinder, general axisymmetric and general surface windows and is currently operational on a VAX 8600 computer system.

Decoding the genome beyond sequencing: the new phase of genomic research.

PubMed

Heng, Henry H Q; Liu, Guo; Stevens, Joshua B; Bremer, Steven W; Ye, Karen J; Abdallah, Batoul Y; Horne, Steven D; Ye, Christine J

2011-10-01

While our understanding of gene-based biology has greatly improved, it is clear that the function of the genome and most diseases cannot be fully explained by genes and other regulatory elements. Genes and the genome represent distinct levels of genetic organization with their own coding systems; Genes code parts like protein and RNA, but the genome codes the structure of genetic networks, which are defined by the whole set of genes, chromosomes and their topological interactions within a cell. Accordingly, the genetic code of DNA offers limited understanding of genome functions. In this perspective, we introduce the genome theory which calls for the departure of gene-centric genomic research. To make this transition for the next phase of genomic research, it is essential to acknowledge the importance of new genome-based biological concepts and to establish new technology platforms to decode the genome beyond sequencing. Copyright © 2011 Elsevier Inc. All rights reserved.

Use of fluorescent proteins and color-coded imaging to visualize cancer cells with different genetic properties.

PubMed

Hoffman, Robert M

2016-03-01

Fluorescent proteins are very bright and available in spectrally-distinct colors, enable the imaging of color-coded cancer cells growing in vivo and therefore the distinction of cancer cells with different genetic properties. Non-invasive and intravital imaging of cancer cells with fluorescent proteins allows the visualization of distinct genetic variants of cancer cells down to the cellular level in vivo. Cancer cells with increased or decreased ability to metastasize can be distinguished in vivo. Gene exchange in vivo which enables low metastatic cancer cells to convert to high metastatic can be color-coded imaged in vivo. Cancer stem-like and non-stem cells can be distinguished in vivo by color-coded imaging. These properties also demonstrate the vast superiority of imaging cancer cells in vivo with fluorescent proteins over photon counting of luciferase-labeled cancer cells.

JURASSIC Retrieval Processing

NASA Astrophysics Data System (ADS)

Blank, J.; Ungermann, J.; Guggenmoser, T.; Kaufmann, M.; Riese, M.

2012-04-01

The Gimballed Limb Observer for Radiance Imaging in the Atmosphere (GLORIA) is an aircraft based infrared limb-sounder. This presentation will give an overview of the retrieval techniques used for the analysis of data produced by the GLORIA instrument. For data processing, the JUelich RApid Spectral SImulation Code 2 (JURASSIC2) was developed. It consists of a set of programs to retrieve atmospheric profiles from GLORIA measurements. The GLORIA Michelson interferometer can run with a wide range of parameters. In the dynamics mode, spectra are generate with a medium spectral and a very high temporal and spatial resolution. Each sample can contain thousands of spectral lines for each contributing trace gas. In the JURASSIC retrieval code this is handled by using a radiative transport model based on the Emissivity Growth Approximation. Deciding which samples should be included in the retrieval is a non-trivial task and requires specific domain knowledge. To ease this problem we developed an automatic selection program by analysing the Shannon information content. By taking into account data for all relevant trace gases and instrument effects, optimal integrated spectral windows are computed. This includes considerations for cross-influence of trace gases, which has non-obvious consequence for the contribution of spectral samples. We developed methods to assess the influence of spectral windows on the retrieval. While we can not exhaustively search the whole range of possible spectral sample combinations, it is possible to optimize information content using a genetic algorithm. The GLORIA instrument is mounted with a viewing direction perpendicular to the flight direction. A gimbal frame makes it possible to move the instrument 45° to both direction. By flying on a circular path, it is possible to generate images of an area of interest from a wide range of angles. These can be analyzed in a 3D-tomographic fashion, which yields superior spatial resolution along line of site. Usually limb instruments have a resolution of several hundred kilometers. In studies we have shown to get a resolution of 35km in all horizontal directions. Even when only linear flight patterns can be realized, resolutions of ≈70km can be obtained. This technique can be used to observe features of the Upper Troposphere Lower Stratosphere (UTLS), where important mixing processes take place. Especially tropopause folds are difficult to image, as their main features need to be along line of flight when using common 1D approach.

Was Wright Right? The Canonical Genetic Code is an Empirical Example of an Adaptive Peak in Nature; Deviant Genetic Codes Evolved Using Adaptive Bridges

PubMed Central

2010-01-01

The canonical genetic code is on a sub-optimal adaptive peak with respect to its ability to minimize errors, and is close to, but not quite, optimal. This is demonstrated by the near-total adjacency of synonymous codons, the similarity of adjacent codons, and comparisons of frequency of amino acid usage with number of codons in the code for each amino acid. As a rare empirical example of an adaptive peak in nature, it shows adaptive peaks are real, not merely theoretical. The evolution of deviant genetic codes illustrates how populations move from a lower to a higher adaptive peak. This is done by the use of “adaptive bridges,” neutral pathways that cross over maladaptive valleys by virtue of masking of the phenotypic expression of some maladaptive aspects in the genotype. This appears to be the general mechanism by which populations travel from one adaptive peak to another. There are multiple routes a population can follow to cross from one adaptive peak to another. These routes vary in the probability that they will be used, and this probability is determined by the number and nature of the mutations that happen along each of the routes. A modification of the depiction of adaptive landscapes showing genetic distances and probabilities of travel along their multiple possible routes would throw light on this important concept. PMID:20711776

Computation of the Genetic Code

NASA Astrophysics Data System (ADS)

Kozlov, Nicolay N.; Kozlova, Olga N.

2018-03-01

One of the problems in the development of mathematical theory of the genetic code (summary is presented in [1], the detailed -to [2]) is the problem of the calculation of the genetic code. Similar problems in the world is unknown and could be delivered only in the 21st century. One approach to solving this problem is devoted to this work. For the first time provides a detailed description of the method of calculation of the genetic code, the idea of which was first published earlier [3]), and the choice of one of the most important sets for the calculation was based on an article [4]. Such a set of amino acid corresponds to a complete set of representations of the plurality of overlapping triple gene belonging to the same DNA strand. A separate issue was the initial point, triggering an iterative search process all codes submitted by the initial data. Mathematical analysis has shown that the said set contains some ambiguities, which have been founded because of our proposed compressed representation of the set. As a result, the developed method of calculation was limited to the two main stages of research, where the first stage only the of the area were used in the calculations. The proposed approach will significantly reduce the amount of computations at each step in this complex discrete structure.

Laser Ray Tracing in a Parallel Arbitrary Lagrangian-Eulerian Adaptive Mesh Refinement Hydrocode

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

Masters, N D; Kaiser, T B; Anderson, R W

2009-09-28

ALE-AMR is a new hydrocode that we are developing as a predictive modeling tool for debris and shrapnel formation in high-energy laser experiments. In this paper we present our approach to implementing laser ray-tracing in ALE-AMR. We present the equations of laser ray tracing, our approach to efficient traversal of the adaptive mesh hierarchy in which we propagate computational rays through a virtual composite mesh consisting of the finest resolution representation of the modeled space, and anticipate simulations that will be compared to experiments for code validation.

Coding of Class I and II aminoacyl-tRNA synthetases

PubMed Central

Carter, Charles W.

2018-01-01

SUMMARY The aminoacyl-tRNA synthetases and their cognate transfer RNAs translate the universal genetic code. The twenty canonical amino acids are sufficiently diverse to create a selective advantage for dividing amino acid activation between two distinct, apparently unrelated superfamilies of synthetases, Class I amino acids being generally larger and less polar, Class II amino acids smaller and more polar. Biochemical, bioinformatic, and protein engineering experiments support the hypothesis that the two Classes descended from opposite strands of the same ancestral gene. Parallel experimental deconstructions of Class I and II synthetases reveal parallel losses in catalytic proficiency at two novel modular levels—protozymes and Urzymes—associated with the evolution of catalytic activity. Bi-directional coding supports an important unification of the proteome; affords a genetic relatedness metric—middle base-pairing frequencies in sense/antisense alignments—that probes more deeply into the evolutionary history of translation than do single multiple sequence alignments; and has facilitated the analysis of hitherto unknown coding relationships in tRNA sequences. Reconstruction of native synthetases by modular thermodynamic cycles facilitated by domain engineering emphasizes the subtlety associated with achieving high specificity, shedding new light on allosteric relationships in contemporary synthetases. Synthetase Urzyme structural biology suggests that they are catalytically active molten globules, broadening the potential manifold of polypeptide catalysts accessible to primitive genetic coding and motivating revisions of the origins of catalysis. Finally, bi-directional genetic coding of some of the oldest genes in the proteome places major limitations on the likelihood that any RNA World preceded the origins of coded proteins. PMID:28828732

Wood construction codes issues in the United States

Treesearch

Douglas R. Rammer

2006-01-01

The current wood construction codes find their origin in the 1935 Wood Handbook: Wood as an Engineering Material published by the USDA Forest Service. Many of the current design recommendations can be traced back to statements from this book. Since this time a series of development both historical and recent has led to a multi-layered system for use of wood products in...

The lack of foundation in the mechanism on which are based the physico-chemical theories for the origin of the genetic code is counterposed to the credible and natural mechanism suggested by the coevolution theory.

PubMed

Di Giulio, Massimo

2016-06-21

I analyze the mechanism on which are based the majority of theories that put to the center of the origin of the genetic code the physico-chemical properties of amino acids. As this mechanism is based on excessive mutational steps, I conclude that it could not have been operative or if operative it would not have allowed a full realization of predictions of these theories, because this mechanism contained, evidently, a high indeterminacy. I make that disapproving the four-column theory of the origin of the genetic code (Higgs, 2009) and reply to the criticism that was directed towards the coevolution theory of the origin of the genetic code. In this context, I suggest a new hypothesis that clarifies the mechanism by which the domains of codons of the precursor amino acids would have evolved, as predicted by the coevolution theory. This mechanism would have used particular elongation factors that would have constrained the evolution of all amino acids belonging to a given biosynthetic family to the progenitor pre-tRNA, that for first recognized, the first codons that evolved in a certain codon domain of a determined precursor amino acid. This happened because the elongation factors recognized two characteristics of the progenitor pre-tRNAs of precursor amino acids, which prevented the elongation factors from recognizing the pre-tRNAs belonging to biosynthetic families of different precursor amino acids. Finally, I analyze by means of Fisher's exact test, the distribution, within the genetic code, of the biosynthetic classes of amino acids and the ones of polarity values of amino acids. This analysis would seem to support the biosynthetic classes of amino acids over the ones of polarity values, as the main factor that led to the structuring of the genetic code, with the physico-chemical properties of amino acids playing only a subsidiary role in this evolution. As a whole, the full analysis brings to the conclusion that the coevolution theory of the origin of the genetic code would be a theory highly corroborated. Copyright © 2016 Elsevier Ltd. All rights reserved.

On initial Brain Activity Mapping of episodic and semantic memory code in the hippocampus.

PubMed

Tsien, Joe Z; Li, Meng; Osan, Remus; Chen, Guifen; Lin, Longian; Wang, Phillip Lei; Frey, Sabine; Frey, Julietta; Zhu, Dajiang; Liu, Tianming; Zhao, Fang; Kuang, Hui

2013-10-01

It has been widely recognized that the understanding of the brain code would require large-scale recording and decoding of brain activity patterns. In 2007 with support from Georgia Research Alliance, we have launched the Brain Decoding Project Initiative with the basic idea which is now similarly advocated by BRAIN project or Brain Activity Map proposal. As the planning of the BRAIN project is currently underway, we share our insights and lessons from our efforts in mapping real-time episodic memory traces in the hippocampus of freely behaving mice. We show that appropriate large-scale statistical methods are essential to decipher and measure real-time memory traces and neural dynamics. We also provide an example of how the carefully designed, sometime thinking-outside-the-box, behavioral paradigms can be highly instrumental to the unraveling of memory-coding cell assembly organizing principle in the hippocampus. Our observations to date have led us to conclude that the specific-to-general categorical and combinatorial feature-coding cell assembly mechanism represents an emergent property for enabling the neural networks to generate and organize not only episodic memory, but also semantic knowledge and imagination. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

On Initial Brain Activity Mapping of Associative Memory Code in the Hippocampus

PubMed Central

Tsien, Joe Z.; Li, Meng; Osan, Remus; Chen, Guifen; Lin, Longian; Lei Wang, Phillip; Frey, Sabine; Frey, Julietta; Zhu, Dajiang; Liu, Tianming; Zhao, Fang; Kuang, Hui

2013-01-01

It has been widely recognized that the understanding of the brain code would require large-scale recording and decoding of brain activity patterns. In 2007 with support from Georgia Research Alliance, we have launched the Brain Decoding Project Initiative with the basic idea which is now similarly advocated by BRAIN project or Brain Activity Map proposal. As the planning of the BRAIN project is currently underway, we share our insights and lessons from our efforts in mapping real-time episodic memory traces in the hippocampus of freely behaving mice. We show that appropriate large-scale statistical methods are essential to decipher and measure real-time memory traces and neural dynamics. We also provide an example of how the carefully designed, sometime thinking-outside-the-box, behavioral paradigms can be highly instrumental to the unraveling of memory-coding cell assembly organizing principle in the hippocampus. Our observations to date have led us to conclude that the specific-to-general categorical and combinatorial feature-coding cell assembly mechanism represents an emergent property for enabling the neural networks to generate and organize not only episodic memory, but also semantic knowledge and imagination. PMID:23838072

TRANSP: status and planning

NASA Astrophysics Data System (ADS)

Andre, R.; Carlsson, J.; Gorelenkova, M.; Jardin, S.; Kaye, S.; Poli, F.; Yuan, X.

2016-10-01

TRANSP is an integrated interpretive and predictive transport analysis tool that incorporates state of the art heating/current drive sources and transport models. The treatments and transport solvers are becoming increasingly sophisticated and comprehensive. For instance, the ISOLVER component provides a free boundary equilibrium solution, while the PT- SOLVER transport solver is especially suited for stiff transport models such as TGLF. TRANSP incorporates high fidelity heating and current drive source models, such as NUBEAM for neutral beam injection, the beam tracing code TORBEAM for EC, TORIC for ICRF, the ray tracing TORAY and GENRAY for EC. The implementation of selected components makes efficient use of MPI for speed up of code calculations. Recently the GENRAY-CQL3D solver for modeling of LH heating and current drive has been implemented and currently being extended to multiple antennas, to allow modeling of EAST discharges. Also, GENRAY+CQL3D is being extended to the use of EC/EBW and of HHFW for NSTX-U. This poster will describe present uses of the code worldwide, as well as plans for upgrading the physics modules and code framework. Work supported by the US Department of Energy under DE-AC02-CH0911466.

Ray-tracing 3D dust radiative transfer with DART-Ray: code upgrade and public release

NASA Astrophysics Data System (ADS)

Natale, Giovanni; Popescu, Cristina C.; Tuffs, Richard J.; Clarke, Adam J.; Debattista, Victor P.; Fischera, Jörg; Pasetto, Stefano; Rushton, Mark; Thirlwall, Jordan J.

2017-11-01

We present an extensively updated version of the purely ray-tracing 3D dust radiation transfer code DART-Ray. The new version includes five major upgrades: 1) a series of optimizations for the ray-angular density and the scattered radiation source function; 2) the implementation of several data and task parallelizations using hybrid MPI+OpenMP schemes; 3) the inclusion of dust self-heating; 4) the ability to produce surface brightness maps for observers within the models in HEALPix format; 5) the possibility to set the expected numerical accuracy already at the start of the calculation. We tested the updated code with benchmark models where the dust self-heating is not negligible. Furthermore, we performed a study of the extent of the source influence volumes, using galaxy models, which are critical in determining the efficiency of the DART-Ray algorithm. The new code is publicly available, documented for both users and developers, and accompanied by several programmes to create input grids for different model geometries and to import the results of N-body and SPH simulations. These programmes can be easily adapted to different input geometries, and for different dust models or stellar emission libraries.

GRay: A Massively Parallel GPU-based Code for Ray Tracing in Relativistic Spacetimes

NASA Astrophysics Data System (ADS)

Chan, Chi-kwan; Psaltis, Dimitrios; Özel, Feryal

2013-11-01

We introduce GRay, a massively parallel integrator designed to trace the trajectories of billions of photons in a curved spacetime. This graphics-processing-unit (GPU)-based integrator employs the stream processing paradigm, is implemented in CUDA C/C++, and runs on nVidia graphics cards. The peak performance of GRay using single-precision floating-point arithmetic on a single GPU exceeds 300 GFLOP (or 1 ns per photon per time step). For a realistic problem, where the peak performance cannot be reached, GRay is two orders of magnitude faster than existing central-processing-unit-based ray-tracing codes. This performance enhancement allows more effective searches of large parameter spaces when comparing theoretical predictions of images, spectra, and light curves from the vicinities of compact objects to observations. GRay can also perform on-the-fly ray tracing within general relativistic magnetohydrodynamic algorithms that simulate accretion flows around compact objects. Making use of this algorithm, we calculate the properties of the shadows of Kerr black holes and the photon rings that surround them. We also provide accurate fitting formulae of their dependencies on black hole spin and observer inclination, which can be used to interpret upcoming observations of the black holes at the center of the Milky Way, as well as M87, with the Event Horizon Telescope.

Genetic Recombination Between Stromal and Cancer Cells Results in Highly Malignant Cells Identified by Color-Coded Imaging in a Mouse Lymphoma Model.

PubMed

Nakamura, Miki; Suetsugu, Atsushi; Hasegawa, Kousuke; Matsumoto, Takuro; Aoki, Hitomi; Kunisada, Takahiro; Shimizu, Masahito; Saji, Shigetoyo; Moriwaki, Hisataka; Hoffman, Robert M

2017-12-01

The tumor microenvironment (TME) promotes tumor growth and metastasis. We previously established the color-coded EL4 lymphoma TME model with red fluorescent protein (RFP) expressing EL4 implanted in transgenic C57BL/6 green fluorescent protein (GFP) mice. Color-coded imaging of the lymphoma TME suggested an important role of stromal cells in lymphoma progression and metastasis. In the present study, we used color-coded imaging of RFP-lymphoma cells and GFP stromal cells to identify yellow-fluorescent genetically recombinant cells appearing only during metastasis. The EL4-RFP lymphoma cells were injected subcutaneously in C57BL/6-GFP transgenic mice and formed subcutaneous tumors 14 days after cell transplantation. The subcutaneous tumors were harvested and transplanted to the abdominal cavity of nude mice. Metastases to the liver, perigastric lymph node, ascites, bone marrow, and primary tumor were imaged. In addition to EL4-RFP cells and GFP-host cells, genetically recombinant yellow-fluorescent cells, were observed only in the ascites and bone marrow. These results indicate genetic exchange between the stromal and cancer cells. Possible mechanisms of genetic exchange are discussed as well as its ramifications for metastasis. J. Cell. Biochem. 118: 4216-4221, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Non-redundant coding of aversive odours in the main olfactory pathway

PubMed Central

Dewan, Adam; Pacifico, Rodrigo; Zhan, Ross; Rinberg, Dmitry; Bozza, Thomas

2013-01-01

Many species are critically dependent on olfaction for survival. In the main olfactory system of mammals, odours are detected by sensory neurons which express a large repertoire of canonical odorant receptors (ORs) and a much smaller repertoire of Trace Amine-Associated Receptors (TAARs)1–4. Odours are encoded in a combinatorial fashion across glomeruli in the main olfactory bulb, with each glomerulus corresponding to a different receptor5–7. The degree to which individual receptor genes contribute to odour perception is unclear. Here we show that genetic deletion of the olfactory TAAR gene family, or even a single TAAR gene, eliminates aversion that mice display to low concentrations of volatile amines and to the odour of predator urine. Our findings identify a role for the TAARs in olfaction, namely in the high-sensitivity detection of innately aversive odours. In addition, our data reveal that aversive amines are represented in a non-redundant fashion, and that individual main olfactory receptor genes can contribute significantly to odour perception. PMID:23624375

Non-redundant coding of aversive odours in the main olfactory pathway.

PubMed

Dewan, Adam; Pacifico, Rodrigo; Zhan, Ross; Rinberg, Dmitry; Bozza, Thomas

2013-05-23

Many species are critically dependent on olfaction for survival. In the main olfactory system of mammals, odours are detected by sensory neurons that express a large repertoire of canonical odorant receptors and a much smaller repertoire of trace amine-associated receptors (TAARs). Odours are encoded in a combinatorial fashion across glomeruli in the main olfactory bulb, with each glomerulus corresponding to a specific receptor. The degree to which individual receptor genes contribute to odour perception is unclear. Here we show that genetic deletion of the olfactory Taar gene family, or even a single Taar gene (Taar4), eliminates the aversion that mice display to low concentrations of volatile amines and to the odour of predator urine. Our findings identify a role for the TAARs in olfaction, namely, in the high-sensitivity detection of innately aversive odours. In addition, our data reveal that aversive amines are represented in a non-redundant fashion, and that individual main olfactory receptor genes can contribute substantially to odour perception.

Can genetics help us understand Indian social history?

PubMed

Thapar, Romila

2014-06-26

Attempts have been made recently to determine the identity of the so-called "Aryans" as components of the Indian population by using DNA analysis. This is largely to ascertain whether they were indigenous to India or were foreign arrivals. Similar attempts have been made to trace the origins of caste groups on the basis of varna identities and record their distribution. The results so far have been contradictory and, therefore, not of much help to social historians. There are problems in the defining of categories and the techniques of analysis. Aryan is a linguistic and cultural category and not a biological one. Caste groups have no well-defined and invariable boundaries despite marriage codes. Various other categories have been assimilated into particular castes as part of the evolution of social history on the subcontinent. A few examples of these are discussed. The problems with using DNA analysis are also touched on. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

A new coding system for metabolic disorders demonstrates gaps in the international disease classifications ICD-10 and SNOMED-CT, which can be barriers to genotype-phenotype data sharing.

PubMed

Sollie, Annet; Sijmons, Rolf H; Lindhout, Dick; van der Ploeg, Ans T; Rubio Gozalbo, M Estela; Smit, G Peter A; Verheijen, Frans; Waterham, Hans R; van Weely, Sonja; Wijburg, Frits A; Wijburg, Rudolph; Visser, Gepke

2013-07-01

Data sharing is essential for a better understanding of genetic disorders. Good phenotype coding plays a key role in this process. Unfortunately, the two most widely used coding systems in medicine, ICD-10 and SNOMED-CT, lack information necessary for the detailed classification and annotation of rare and genetic disorders. This prevents the optimal registration of such patients in databases and thus data-sharing efforts. To improve care and to facilitate research for patients with metabolic disorders, we developed a new coding system for metabolic diseases with a dedicated group of clinical specialists. Next, we compared the resulting codes with those in ICD and SNOMED-CT. No matches were found in 76% of cases in ICD-10 and in 54% in SNOMED-CT. We conclude that there are sizable gaps in the SNOMED-CT and ICD coding systems for metabolic disorders. There may be similar gaps for other classes of rare and genetic disorders. We have demonstrated that expert groups can help in addressing such coding issues. Our coding system has been made available to the ICD and SNOMED-CT organizations as well as to the Orphanet and HPO organizations for further public application and updates will be published online (www.ddrmd.nl and www.cineas.org). © 2013 WILEY PERIODICALS, INC.

System and method for deriving a process-based specification

NASA Technical Reports Server (NTRS)

Hinchey, Michael Gerard (Inventor); Rouff, Christopher A. (Inventor); Rash, James Larry (Inventor)

2009-01-01

A system and method for deriving a process-based specification for a system is disclosed. The process-based specification is mathematically inferred from a trace-based specification. The trace-based specification is derived from a non-empty set of traces or natural language scenarios. The process-based specification is mathematically equivalent to the trace-based specification. Code is generated, if applicable, from the process-based specification. A process, or phases of a process, using the features disclosed can be reversed and repeated to allow for an interactive development and modification of legacy systems. The process is applicable to any class of system, including, but not limited to, biological and physical systems, electrical and electro-mechanical systems in addition to software, hardware and hybrid hardware-software systems.

Expanding the genetic code for site-specific labelling of tobacco mosaic virus coat protein and building biotin-functionalized virus-like particles.

PubMed

Wu, F C; Zhang, H; Zhou, Q; Wu, M; Ballard, Z; Tian, Y; Wang, J Y; Niu, Z W; Huang, Y

2014-04-18

A method for site-specific and high yield modification of tobacco mosaic virus coat protein (TMVCP) utilizing a genetic code expanding technology and copper free cycloaddition reaction has been established, and biotin-functionalized virus-like particles were built by the self-assembly of the protein monomers.

On origin of genetic code and tRNA before translation

PubMed Central

2011-01-01

Background Synthesis of proteins is based on the genetic code - a nearly universal assignment of codons to amino acids (aas). A major challenge to the understanding of the origins of this assignment is the archetypal "key-lock vs. frozen accident" dilemma. Here we re-examine this dilemma in light of 1) the fundamental veto on "foresight evolution", 2) modular structures of tRNAs and aminoacyl-tRNA synthetases, and 3) the updated library of aa-binding sites in RNA aptamers successfully selected in vitro for eight amino acids. Results The aa-binding sites of arginine, isoleucine and tyrosine contain both their cognate triplets, anticodons and codons. We have noticed that these cases might be associated with palindrome-dinucleotides. For example, one-base shift to the left brings arginine codons CGN, with CG at 1-2 positions, to the respective anticodons NCG, with CG at 2-3 positions. Formally, the concomitant presence of codons and anticodons is also expected in the reverse situation, with codons containing palindrome-dinucleotides at their 2-3 positions, and anticodons exhibiting them at 1-2 positions. A closer analysis reveals that, surprisingly, RNA binding sites for Arg, Ile and Tyr "prefer" (exactly as in the actual genetic code) the anticodon(2-3)/codon(1-2) tetramers to their anticodon(1-2)/codon(2-3) counterparts, despite the seemingly perfect symmetry of the latter. However, since in vitro selection of aa-specific RNA aptamers apparently had nothing to do with translation, this striking preference provides a new strong support to the notion of the genetic code emerging before translation, in response to catalytic (and possibly other) needs of ancient RNA life. Consistently with the pre-translation origin of the code, we propose here a new model of tRNA origin by the gradual, Fibonacci process-like, elongation of a tRNA molecule from a primordial coding triplet and 5'DCCA3' quadruplet (D is a base-determinator) to the eventual 76 base-long cloverleaf-shaped molecule. Conclusion Taken together, our findings necessarily imply that primordial tRNAs, tRNA aminoacylating ribozymes, and (later) the translation machinery in general have been co-evolving to ''fit'' the (likely already defined) genetic code, rather than the opposite way around. Coding triplets in this primal pre-translational code were likely similar to the anticodons, with second and third nucleotides being more important than the less specific first one. Later, when the code was expanding in co-evolution with the translation apparatus, the importance of 2-3 nucleotides of coding triplets "transferred" to the 1-2 nucleotides of their complements, thus distinguishing anticodons from codons. This evolutionary primacy of anticodons in genetic coding makes the hypothesis of primal stereo-chemical affinity between amino acids and cognate triplets, the hypothesis of coding coenzyme handles for amino acids, the hypothesis of tRNA-like genomic 3' tags suggesting that tRNAs originated in replication, and the hypothesis of ancient ribozymes-mediated operational code of tRNA aminoacylation not mutually contradicting but rather co-existing in harmony. Reviewers This article was reviewed by Eugene V. Koonin, Wentao Ma (nominated by Juergen Brosius) and Anthony Poole. PMID:21342520

Genetic code mutations: the breaking of a three billion year invariance.

PubMed

Mat, Wai-Kin; Xue, Hong; Wong, J Tze-Fei

2010-08-20

The genetic code has been unchanging for some three billion years in its canonical ensemble of encoded amino acids, as indicated by the universal adoption of this ensemble by all known organisms. Code mutations beginning with the encoding of 4-fluoro-Trp by Bacillus subtilis, initially replacing and eventually displacing Trp from the ensemble, first revealed the intrinsic mutability of the code. This has since been confirmed by a spectrum of other experimental code alterations in both prokaryotes and eukaryotes. To shed light on the experimental conversion of a rigidly invariant code to a mutating code, the present study examined code mutations determining the propagation of Bacillus subtilis on Trp and 4-, 5- and 6-fluoro-tryptophans. The results obtained with the mutants with respect to cross-inhibitions between the different indole amino acids, and the growth effects of individual nutrient withdrawals rendering essential their biosynthetic pathways, suggested that oligogenic barriers comprising sensitive proteins which malfunction with amino acid analogues provide effective mechanisms for preserving the invariance of the code through immemorial time, and mutations of these barriers open up the code to continuous change.

Worldwide genetic diversity for mineral element concentrations in rice grain

USDA-ARS?s Scientific Manuscript database

With the aim of identifying rice (Oryza spp.) germplasm having enhanced grain nutritional value, the mineral nutrient and trace element content (a.k.a. ionome) of whole (unmilled) grains from a set of 1763 rice accessions of diverse geographic and genetic origin were evaluated. Seed for analysis o...

Digital Isotope Coding to Trace the Growth Process of Individual Single-Walled Carbon Nanotubes.

PubMed

Otsuka, Keigo; Yamamoto, Shun; Inoue, Taiki; Koyano, Bunsho; Ukai, Hiroyuki; Yoshikawa, Ryo; Xiang, Rong; Chiashi, Shohei; Maruyama, Shigeo

2018-04-24

Single-walled carbon nanotubes (SWCNTs) are attracting increasing attention as an ideal material for high-performance electronics through the preparation of arrays of purely semiconducting SWCNTs. Despite significant progress in the controlled synthesis of SWCNTs, their growth mechanism remains unclear due to difficulties in analyzing the time-resolved growth of individual SWCNTs under practical growth conditions. Here we present a method for tracing the diverse growth profiles of individual SWCNTs by embedding digitally coded isotope labels. Raman mapping showed that, after various incubation times, SWCNTs elongated monotonically until their abrupt termination. Ex situ analysis offered an opportunity to capture rare chirality changes along the SWCNTs, which resulted in sudden acceleration/deceleration of the growth rate. Dependence on growth parameters, such as temperature and carbon concentration, was also traced along individual SWCNTs, which could provide clues to chirality control. Systematic growth studies with a variety of catalysts and conditions, which combine the presented method with other characterization techniques, will lead to further understanding and control of chirality, length, and density of SWCNTs.

Particle tracing modeling of ion fluxes at geosynchronous orbit

DOE PAGES

Brito, Thiago V.; Woodroffe, Jesse; Jordanova, Vania K.; ...

2017-10-31

The initial results of a coupled MHD/particle tracing method to evaluate particle fluxes in the inner magnetosphere are presented. This setup is capable of capturing the earthward particle acceleration process resulting from dipolarization events in the tail region of the magnetosphere. On the period of study, the MHD code was able to capture a dipolarization event and the particle tracing algorithm was able to capture our results of these disturbances and calculate proton fluxes in the night side geosynchronous orbit region. The simulation captured dispersionless injections as well as the energy dispersion signatures that are frequently observed by satellites atmore » geosynchronous orbit. Currently, ring current models rely on Maxwellian-type distributions based on either empirical flux values or sparse satellite data for their boundary conditions close to geosynchronous orbit. In spite of some differences in intensity and timing, the setup presented here is able to capture substorm injections, which represents an improvement regarding a reverse way of coupling these ring current models with MHD codes through the use of boundary conditions.« less

Particle tracing modeling of ion fluxes at geosynchronous orbit

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

Brito, Thiago V.; Woodroffe, Jesse; Jordanova, Vania K.

The initial results of a coupled MHD/particle tracing method to evaluate particle fluxes in the inner magnetosphere are presented. This setup is capable of capturing the earthward particle acceleration process resulting from dipolarization events in the tail region of the magnetosphere. On the period of study, the MHD code was able to capture a dipolarization event and the particle tracing algorithm was able to capture our results of these disturbances and calculate proton fluxes in the night side geosynchronous orbit region. The simulation captured dispersionless injections as well as the energy dispersion signatures that are frequently observed by satellites atmore » geosynchronous orbit. Currently, ring current models rely on Maxwellian-type distributions based on either empirical flux values or sparse satellite data for their boundary conditions close to geosynchronous orbit. In spite of some differences in intensity and timing, the setup presented here is able to capture substorm injections, which represents an improvement regarding a reverse way of coupling these ring current models with MHD codes through the use of boundary conditions.« less

Transient analysis of ”2 inch Direct Vessel Injection line break” in SPES-2 facility by using TRACE code

NASA Astrophysics Data System (ADS)

D'Amico, S.; Lombardo, C.; Moscato, I.; Polidori, M.; Vella, G.

2015-11-01

In the past few decades a lot of theoretical and experimental researches have been done to understand the physical phenomena characterizing nuclear accidents. In particular, after the Three Miles Island accident, several reactors have been designed to handle successfully LOCA events. This paper presents a comparison between experimental and numerical results obtained for the “2 inch Direct Vessel Injection line break” in SPES-2. This facility is an integral test facility built in Piacenza at the SIET laboratories and simulating the primary circuit, the relevant parts of the secondary circuits and the passive safety systems typical of the AP600 nuclear power plant. The numerical analysis here presented was performed by using TRACE and CATHARE thermal-hydraulic codes with the purpose of evaluating their prediction capability. The main results show that the TRACE model well predicts the overall behaviour of the plant during the transient, in particular it is able to simulate the principal thermal-hydraulic phenomena related to all passive safety systems. The performance of the presented CATHARE noding has suggested some possible improvements of the model.

On the Evolution of the Standard Genetic Code: Vestiges of Critical Scale Invariance from the RNA World in Current Prokaryote Genomes

PubMed Central

José, Marco V.; Govezensky, Tzipe; García, José A.; Bobadilla, Juan R.

2009-01-01

Herein two genetic codes from which the primeval RNA code could have originated the standard genetic code (SGC) are derived. One of them, called extended RNA code type I, consists of all codons of the type RNY (purine-any base-pyrimidine) plus codons obtained by considering the RNA code but in the second (NYR type) and third (YRN type) reading frames. The extended RNA code type II, comprises all codons of the type RNY plus codons that arise from transversions of the RNA code in the first (YNY type) and third (RNR) nucleotide bases. In order to test if putative nucleotide sequences in the RNA World and in both extended RNA codes, share the same scaling and statistical properties to those encountered in current prokaryotes, we used the genomes of four Eubacteria and three Archaeas. For each prokaryote, we obtained their respective genomes obeying the RNA code or the extended RNA codes types I and II. In each case, we estimated the scaling properties of triplet sequences via a renormalization group approach, and we calculated the frequency distributions of distances for each codon. Remarkably, the scaling properties of the distance series of some codons from the RNA code and most codons from both extended RNA codes turned out to be identical or very close to the scaling properties of codons of the SGC. To test for the robustness of these results, we show, via computer simulation experiments, that random mutations of current genomes, at the rates of 10−10 per site per year during three billions of years, were not enough for destroying the observed patterns. Therefore, we conclude that most current prokaryotes may still contain relics of the primeval RNA World and that both extended RNA codes may well represent two plausible evolutionary paths between the RNA code and the current SGC. PMID:19183813

[Genetic diversity analysis of Andrographis paniculata in China based on SRAP and SNP].

PubMed

Chen, Rong; Wang, Xiao-Yun; Song, Yu-Ning; Zhu, Yun-feng; Wang, Peng-liang; Li, Min; Zhong, Guo-Yue

2014-12-01

In order to reveal genetic diversity of domestic Andrographis paniculata and its impact on quality, genetic backgrounds of 103 samples from 7 provinces in China were analyzed using SRAP marker and SNP marker. Genetic structures of the A. paniculata populations were estimated with Powermarker V 3.25 and Mega 6.0 software, and polymorphic SNPs were identified with CodonCode Aligner software. The results showed that the genetic distances of domestic A. paniculata germplasm ranged from 0. 01 to 0.09, and no polymorphic SNPs were discovered in coding sequence fragments of ent-copalyl diphosphate synthase. A. paniculata germplasm from various regions in China had poor genetic diversity. This phenomenon was closely related to strict self-fertilization and earlier introduction from the same origin. Therefore, genetic background had little impact on variable qualities of A. paniculata in domestic market. Mutation breeding, polyploid breeding and molecular breeding were proposed as promising strategies in germplasm innovation.

Optimization of algorithm of coding of genetic information of Chlamydia

NASA Astrophysics Data System (ADS)

Feodorova, Valentina A.; Ulyanov, Sergey S.; Zaytsev, Sergey S.; Saltykov, Yury V.; Ulianova, Onega V.

2018-04-01

New method of coding of genetic information using coherent optical fields is developed. Universal technique of transformation of nucleotide sequences of bacterial gene into laser speckle pattern is suggested. Reference speckle patterns of the nucleotide sequences of omp1 gene of typical wild strains of Chlamydia trachomatis of genovars D, E, F, G, J and K and Chlamydia psittaci serovar I as well are generated. Algorithm of coding of gene information into speckle pattern is optimized. Fully developed speckles with Gaussian statistics for gene-based speckles have been used as criterion of optimization.

Evaluating progressive-rendering algorithms in appearance design tasks.

PubMed

Jiawei Ou; Karlik, Ondrej; Křivánek, Jaroslav; Pellacini, Fabio

2013-01-01

Progressive rendering is becoming a popular alternative to precomputational approaches to appearance design. However, progressive algorithms create images exhibiting visual artifacts at early stages. A user study investigated these artifacts' effects on user performance in appearance design tasks. Novice and expert subjects performed lighting and material editing tasks with four algorithms: random path tracing, quasirandom path tracing, progressive photon mapping, and virtual-point-light rendering. Both the novices and experts strongly preferred path tracing to progressive photon mapping and virtual-point-light rendering. None of the participants preferred random path tracing to quasirandom path tracing or vice versa; the same situation held between progressive photon mapping and virtual-point-light rendering. The user workflow didn’t differ significantly with the four algorithms. The Web Extras include a video showing how four progressive-rendering algorithms converged (at http://youtu.be/ck-Gevl1e9s), the source code used, and other supplementary materials.

Xenomicrobiology: a roadmap for genetic code engineering.

PubMed

Acevedo-Rocha, Carlos G; Budisa, Nediljko

2016-09-01

Biology is an analytical and informational science that is becoming increasingly dependent on chemical synthesis. One example is the high-throughput and low-cost synthesis of DNA, which is a foundation for the research field of synthetic biology (SB). The aim of SB is to provide biotechnological solutions to health, energy and environmental issues as well as unsustainable manufacturing processes in the frame of naturally existing chemical building blocks. Xenobiology (XB) goes a step further by implementing non-natural building blocks in living cells. In this context, genetic code engineering respectively enables the re-design of genes/genomes and proteins/proteomes with non-canonical nucleic (XNAs) and amino (ncAAs) acids. Besides studying information flow and evolutionary innovation in living systems, XB allows the development of new-to-nature therapeutic proteins/peptides, new biocatalysts for potential applications in synthetic organic chemistry and biocontainment strategies for enhanced biosafety. In this perspective, we provide a brief history and evolution of the genetic code in the context of XB. We then discuss the latest efforts and challenges ahead for engineering the genetic code with focus on substitutions and additions of ncAAs as well as standard amino acid reductions. Finally, we present a roadmap for the directed evolution of artificial microbes for emancipating rare sense codons that could be used to introduce novel building blocks. The development of such xenomicroorganisms endowed with a 'genetic firewall' will also allow to study and understand the relation between code evolution and horizontal gene transfer. © 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Time-Domain Receiver Function Deconvolution using Genetic Algorithm

NASA Astrophysics Data System (ADS)

Moreira, L. P.

2017-12-01

Receiver Functions (RF) are well know method for crust modelling using passive seismological signals. Many different techniques were developed to calculate the RF traces, applying the deconvolution calculation to radial and vertical seismogram components. A popular method used a spectral division of both components, which requires human intervention to apply the Water Level procedure to avoid instabilities from division by small numbers. One of most used method is an iterative procedure to estimate the RF peaks and applying the convolution with vertical component seismogram, comparing the result with the radial component. This method is suitable for automatic processing, however several RF traces are invalid due to peak estimation failure.In this work it is proposed a deconvolution algorithm using Genetic Algorithm (GA) to estimate the RF peaks. This method is entirely processed in the time domain, avoiding the time-to-frequency calculations (and vice-versa), and totally suitable for automatic processing. Estimated peaks can be used to generate RF traces in a seismogram format for visualization. The RF trace quality is similar for high magnitude events, although there are less failures for RF calculation of smaller events, increasing the overall performance for high number of events per station.

A sensitive method to extract DNA from biological traces present on ammunition for the purpose of genetic profiling.

PubMed

Dieltjes, Patrick; Mieremet, René; Zuniga, Sofia; Kraaijenbrink, Thirsa; Pijpe, Jeroen; de Knijff, Peter

2011-07-01

Exploring technological limits is a common practice in forensic DNA research. Reliable genetic profiling based on only a few cells isolated from trace material retrieved from a crime scene is nowadays more and more the rule rather than the exception. On many crime scenes, cartridges, bullets, and casings (jointly abbreviated as CBCs) are regularly found, and even after firing, these potentially carry trace amounts of biological material. Since 2003, the Forensic Laboratory for DNA Research is routinely involved in the forensic investigation of CBCs in the Netherlands. Reliable DNA profiles were frequently obtained from CBCs and used to match suspects, victims, or other crime scene-related DNA traces. In this paper, we describe the sensitive method developed by us to extract DNA from CBCs. Using PCR-based genotyping of autosomal short tandem repeats, we were able to obtain reliable and reproducible DNA profiles in 163 out of 616 criminal cases (26.5%) and in 283 out of 4,085 individual CBC items (6.9%) during the period January 2003-December 2009. We discuss practical aspects of the method and the sometimes unexpected effects of using cell lysis buffer on the subsequent investigation of striation patterns on CBCs.

Color Code: Using Hair Color to Make a Clear Connection between Genotype and Phenotype

ERIC Educational Resources Information Center

Bonner, J. Jose

2011-01-01

Students may wonder why they look the way they do. The answer lies in genetics, the branch of biology that deals with heredity and the variation of inherited traits. However, understanding how an organism's genetic code (i.e., genotype) affects its characteristics (i.e., phenotype) is more than a matter of idle curiosity: It's essential for…

Small non-coding RNAs (sncRNA) regulate gene silencing and modify homeostatic status in animals faced with porcine reproductive and respiratory syndrome virus (PRRSV)

USDA-ARS?s Scientific Manuscript database

It has been established that reduced susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) has a genetic component. This genetic component may take the form of small non-coding RNAs (sncRNA), which are molecules that function as regulators of gene expression. Various sncRNAs ...

The chemical basis for the origin of the genetic code and the process of protein synthesis

NASA Technical Reports Server (NTRS)

1982-01-01

The major thrust is to understand just how the process of protein synthesis, including that very important aspect, genetic coding, came to be. Two aspects of the problem: the chemistry of active aminoacyl species; and affinities between amino acids and nucleotides, and specifically, how these affinities might affect the chemistry between the two are stressed.

Mitochondrial genome evidence reveals successful Late Paleolithic settlement on the Tibetan Plateau

PubMed Central

Zhao, Mian; Kong, Qing-Peng; Wang, Hua-Wei; Peng, Min-Sheng; Xie, Xiao-Dong; Wang, Wen-Zhi; Jiayang; Duan, Jian-Guo; Cai, Ming-Cui; Zhao, Shi-Neng; Cidanpingcuo; Tu, Yuan-Quan; Wu, Shi-Fang; Yao, Yong-Gang; Bandelt, Hans-Jürgen; Zhang, Ya-Ping

2009-01-01

Due to its numerous environmental extremes, the Tibetan Plateau—the world's highest plateau—is one of the most challenging areas of modern human settlement. Archaeological evidence dates the earliest settlement on the plateau to the Late Paleolithic, while previous genetic studies have traced the colonization event(s) to no earlier than the Neolithic. To explore whether the genetic continuity on the plateau has an exclusively Neolithic time depth, we studied mitochondrial DNA (mtDNA) genome variation within 6 regional Tibetan populations sampled from Tibet and neighboring areas. Our results confirm that the vast majority of Tibetan matrilineal components can trace their ancestry to Epipaleolithic and Neolithic immigrants from northern China during the mid-Holocene. Significantly, we also identified an infrequent novel haplogroup, M16, that branched off directly from the Eurasian M founder type. Its nearly exclusive distribution in Tibetan populations and ancient age (>21 kya) suggest that M16 may represent the genetic relics of the Late Paleolithic inhabitants on the plateau. This partial genetic continuity between the Paleolithic inhabitants and the contemporary Tibetan populations bridges the results and inferences from archaeology, history, and genetics. PMID:19955425

Interaction between the Bacterium Pseudomonas fluorescens strain CHA0, its genetic derivatives and vermiculite: Effects on chemical, mineralogical and mechanical properties of vermiculite

NASA Astrophysics Data System (ADS)

Mueller, Barbara

2016-04-01

Using bacteria of the strain Pseudomonas fluorescens wild type CHA0 and its genetic derivative strains CHA77, CHA89, CHA400, CHA631 and CHA661 (which differ in one gene only) the changes in chemical, mineralogical and rheological properties of the clay mineral vermiculite affected by microbial activity were studied in order to test whether the individually different production of metabolites by the genetically engineered strains may alter the clay mineral vermiculite in distinct ways. With the novel strategy of working with living wild type bacteria, their genetic derivatives and clay, the following properties of the mineral altered by the various strains of Pseudomonas fluorescens were determined: grain size, X-Ray diffraction pattern, intercrystalline swelling with glycerol, layer charge, CEC, BET surface and uptake of trace elements. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used to determine the changes in major, minor and trace elements of the clay vermiculite affected by microbial activity. Among all analyzed trace elements, Fe, Mn and Cu are the most interesting. Fe and Mn are taken up from the clay mineral by all bacterial strains whereas Cu is only removed from vermiculite by strains CHA0, CHA77, CHA400 and CHA661. The latter mentioned strains all produce the antibiotics 2,4-diacetylphloroglucinol and monoacetylphloroglucinol which can complex Cu efficiently. Therefore the alteration of only one gene of the bacteria is causing significant effects on the clay mineral.

3D-PDR: Three-dimensional photodissociation region code

NASA Astrophysics Data System (ADS)

Bisbas, T. G.; Bell, T. A.; Viti, S.; Yates, J.; Barlow, M. J.

2018-03-01

3D-PDR is a three-dimensional photodissociation region code written in Fortran. It uses the Sundials package (written in C) to solve the set of ordinary differential equations and it is the successor of the one-dimensional PDR code UCL_PDR (ascl:1303.004). Using the HEALpix ray-tracing scheme (ascl:1107.018), 3D-PDR solves a three-dimensional escape probability routine and evaluates the attenuation of the far-ultraviolet radiation in the PDR and the propagation of FIR/submm emission lines out of the PDR. The code is parallelized (OpenMP) and can be applied to 1D and 3D problems.

The impact of rare variation on gene expression across tissues.

PubMed

Li, Xin; Kim, Yungil; Tsang, Emily K; Davis, Joe R; Damani, Farhan N; Chiang, Colby; Hess, Gaelen T; Zappala, Zachary; Strober, Benjamin J; Scott, Alexandra J; Li, Amy; Ganna, Andrea; Bassik, Michael C; Merker, Jason D; Hall, Ira M; Battle, Alexis; Montgomery, Stephen B

2017-10-11

Rare genetic variants are abundant in humans and are expected to contribute to individual disease risk. While genetic association studies have successfully identified common genetic variants associated with susceptibility, these studies are not practical for identifying rare variants. Efforts to distinguish pathogenic variants from benign rare variants have leveraged the genetic code to identify deleterious protein-coding alleles, but no analogous code exists for non-coding variants. Therefore, ascertaining which rare variants have phenotypic effects remains a major challenge. Rare non-coding variants have been associated with extreme gene expression in studies using single tissues, but their effects across tissues are unknown. Here we identify gene expression outliers, or individuals showing extreme expression levels for a particular gene, across 44 human tissues by using combined analyses of whole genomes and multi-tissue RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project v6p release. We find that 58% of underexpression and 28% of overexpression outliers have nearby conserved rare variants compared to 8% of non-outliers. Additionally, we developed RIVER (RNA-informed variant effect on regulation), a Bayesian statistical model that incorporates expression data to predict a regulatory effect for rare variants with higher accuracy than models using genomic annotations alone. Overall, we demonstrate that rare variants contribute to large gene expression changes across tissues and provide an integrative method for interpretation of rare variants in individual genomes.

On the evolution of primitive genetic codes.

PubMed

Weberndorfer, Günter; Hofacker, Ivo L; Stadler, Peter F

2003-10-01

The primordial genetic code probably has been a drastically simplified ancestor of the canonical code that is used by contemporary cells. In order to understand how the present-day code came about we first need to explain how the language of the building plan can change without destroying the encoded information. In this work we introduce a minimal organism model that is based on biophysically reasonable descriptions of RNA and protein, namely secondary structure folding and knowledge based potentials. The evolution of a population of such organism under competition for a common resource is simulated explicitly at the level of individual replication events. Starting with very simple codes, and hence greatly reduced amino acid alphabets, we observe a diversification of the codes in most simulation runs. The driving force behind this effect is the possibility to produce fitter proteins when the repertoire of amino acids is enlarged.

TraceContract

NASA Technical Reports Server (NTRS)

Kavelund, Klaus; Barringer, Howard

2012-01-01

TraceContract is an API (Application Programming Interface) for trace analysis. A trace is a sequence of events, and can, for example, be generated by a running program, instrumented appropriately to generate events. An event can be any data object. An example of a trace is a log file containing events that a programmer has found important to record during a program execution. Trace - Contract takes as input such a trace together with a specification formulated using the API and reports on any violations of the specification, potentially calling code (reactions) to be executed when violations are detected. The software is developed as an internal DSL (Domain Specific Language) in the Scala programming language. Scala is a relatively new programming language that is specifically convenient for defining such internal DSLs due to a number of language characteristics. This includes Scala s elegant combination of object-oriented and functional programming, a succinct notation, and an advanced type system. The DSL offers a combination of data-parameterized state machines and temporal logic, which is novel. As an extension of Scala, it is a very expressive and convenient log file analysis framework.

Genetics of Inflammatory Bowel Diseases

PubMed Central

McGovern, Dermot; Kugathasan, Subra; Cho, Judy H.

2015-01-01

In this Review, we provide an update on genome-wide association studies (GWAS) in inflammatory bowel disease (IBD). In addition, we summarize progress in defining the functional consequences of associated alleles for coding and non-coding genetic variation. In the small minority of loci where major association signals correspond to non-synonymous variation, we summarize studies defining their functional effects and implications for therapeutic targeting. Importantly, the large majority of GWAS-associated loci involve non-coding variation, many of which modulate levels of gene expression. Recent expression quantitative trait loci (eQTL) studies have established that expression of the large majority of human genes is regulated by non-coding genetic variation. Significant advances in defining the epigenetic landscape have demonstrated that IBD GWAS signals are highly enriched within cell-specific active enhancer marks. Studies in European ancestry populations have dominated the landscape of IBD genetics studies, but increasingly, studies in Asian and African-American populations are being reported. Common variation accounts for only a modest fraction of the predicted heritability and the role of rare genetic variation of higher effects (i.e. odds ratios markedly deviating from one) is increasingly being identified through sequencing efforts. These sequencing studies have been particularly productive in very-early onset, more severe cases. A major challenge in IBD genetics will be harnessing the vast array of genetic discovery for clinical utility, through emerging precision medicine initiatives. We discuss the rapidly evolving area of direct to consumer genetic testing, as well as the current utility of clinical exome sequencing, especially in very early onset, severe IBD cases. We summarize recent progress in the pharmacogenetics of IBD with respect of partitioning patient responses to anti-TNF and thiopurine therapies. Highly collaborative studies across research centers and across subspecialties and disciplines will be required to fully realize the promise of genetic discovery in IBD. PMID:26255561

Modeling the Volcanic Source at Long Valley, CA, Using a Genetic Algorithm Technique

NASA Technical Reports Server (NTRS)

Tiampo, Kristy F.

1999-01-01

In this project, we attempted to model the deformation pattern due to the magmatic source at Long Valley caldera using a real-value coded genetic algorithm (GA) inversion similar to that found in Michalewicz, 1992. The project has been both successful and rewarding. The genetic algorithm, coded in the C programming language, performs stable inversions over repeated trials, with varying initial and boundary conditions. The original model used a GA in which the geophysical information was coded into the fitness function through the computation of surface displacements for a Mogi point source in an elastic half-space. The program was designed to invert for a spherical magmatic source - its depth, horizontal location and volume - using the known surface deformations. It also included the capability of inverting for multiple sources.

Saturation of recognition elements blocks evolution of new tRNA identities

PubMed Central

Saint-Léger, Adélaïde; Bello, Carla; Dans, Pablo D.; Torres, Adrian Gabriel; Novoa, Eva Maria; Camacho, Noelia; Orozco, Modesto; Kondrashov, Fyodor A.; Ribas de Pouplana, Lluís

2016-01-01

Understanding the principles that led to the current complexity of the genetic code is a central question in evolution. Expansion of the genetic code required the selection of new transfer RNAs (tRNAs) with specific recognition signals that allowed them to be matured, modified, aminoacylated, and processed by the ribosome without compromising the fidelity or efficiency of protein synthesis. We show that saturation of recognition signals blocks the emergence of new tRNA identities and that the rate of nucleotide substitutions in tRNAs is higher in species with fewer tRNA genes. We propose that the growth of the genetic code stalled because a limit was reached in the number of identity elements that can be effectively used in the tRNA structure. PMID:27386510

Analysis of memory use for improved design and compile-time allocation of local memory

NASA Technical Reports Server (NTRS)

Mcniven, Geoffrey D.; Davidson, Edward S.

1986-01-01

Trace analysis techniques are used to study memory referencing behavior for the purpose of designing local memories and determining how to allocate them for data and instructions. In an attempt to assess the inherent behavior of the source code, the trace analysis system described here reduced the effects of the compiler and host architecture on the trace by using a technical called flattening. The variables in the trace, their associated single-assignment values, and references are histogrammed on the basis of various parameters describing memory referencing behavior. Bounds are developed specifying the amount of memory space required to store all live values in a particular histogram class. The reduction achieved in main memory traffic by allocating local memory is specified for each class.

Evidence-Based Reading and Writing Assessment for Dyslexia in Adolescents and Young Adults

PubMed Central

Nielsen, Kathleen; Abbott, Robert; Griffin, Whitney; Lott, Joe; Raskind, Wendy; Berninger, Virginia W.

2016-01-01

The same working memory and reading and writing achievement phenotypes (behavioral markers of genetic variants) validated in prior research with younger children and older adults in a multi-generational family genetics study of dyslexia were used to study 81 adolescent and young adults (ages 16 to 25) from that study. Dyslexia is impaired word reading and spelling skills below the population mean and ability to use oral language to express thinking. These working memory predictor measures were given and used to predict reading and writing achievement: Coding (storing and processing) heard and spoken words (phonological coding), read and written words (orthographic coding), base words and affixes (morphological coding), and accumulating words over time (syntax coding); Cross-Code Integration (phonological loop for linking phonological name and orthographic letter codes and orthographic loop for linking orthographic letter codes and finger sequencing codes), and Supervisory Attention (focused and switching attention and self-monitoring during written word finding). Multiple regressions showed that most predictors explained individual difference in at least one reading or writing outcome, but which predictors explained unique variance beyond shared variance depended on outcome. ANOVAs confirmed that research-supported criteria for dyslexia validated for younger children and their parents could be used to diagnose which adolescents and young adults did (n=31) or did not (n=50) meet research criteria for dyslexia. Findings are discussed in reference to the heterogeneity of phenotypes (behavioral markers of genetic variables) and their application to assessment for accommodations and ongoing instruction for adolescents and young adults with dyslexia. PMID:26855554

On models of the genetic code generated by binary dichotomic algorithms.

PubMed

Gumbel, Markus; Fimmel, Elena; Danielli, Alberto; Strüngmann, Lutz

2015-02-01

In this paper we introduce the concept of a BDA-generated model of the genetic code which is based on binary dichotomic algorithms (BDAs). A BDA-generated model is based on binary dichotomic algorithms (BDAs). Such a BDA partitions the set of 64 codons into two disjoint classes of size 32 each and provides a generalization of known partitions like the Rumer dichotomy. We investigate what partitions can be generated when a set of different BDAs is applied sequentially to the set of codons. The search revealed that these models are able to generate code tables with very different numbers of classes ranging from 2 to 64. We have analyzed whether there are models that map the codons to their amino acids. A perfect matching is not possible. However, we present models that describe the standard genetic code with only few errors. There are also models that map all 64 codons uniquely to 64 classes showing that BDAs can be used to identify codons precisely. This could serve as a basis for further mathematical analysis using coding theory, for example. The hypothesis that BDAs might reflect a molecular mechanism taking place in the decoding center of the ribosome is discussed. The scan demonstrated that binary dichotomic partitions are able to model different aspects of the genetic code very well. The search was performed with our tool Beady-A. This software is freely available at http://mi.informatik.hs-mannheim.de/beady-a. It requires a JVM version 6 or higher. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Tangled Webs: Tracing the Connections between Genes and Cognition

ERIC Educational Resources Information Center

Fisher, Simon E.

2006-01-01

The rise of molecular genetics is having a pervasive influence in a wide variety of fields, including research into neurodevelopmental disorders like dyslexia, speech and language impairments, and autism. There are many studies underway which are attempting to determine the roles of genetic factors in the aetiology of these disorders. Beyond the…

(U) Second-Order Sensitivity Analysis of Uncollided Particle Contributions to Radiation Detector Responses Using Ray-Tracing

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

Favorite, Jeffrey A.

The Second-Level Adjoint Sensitivity System (2nd-LASS) that yields the second-order sensitivities of a response of uncollided particles with respect to isotope densities, cross sections, and source emission rates is derived in Refs. 1 and 2. In Ref. 2, we solved problems for the uncollided leakage from a homogeneous sphere and a multiregion cylinder using the PARTISN multigroup discrete-ordinates code. In this memo, we derive solutions of the 2nd-LASS for the particular case when the response is a flux or partial current density computed at a single point on the boundary, and the inner products are computed using ray-tracing. Both themore » PARTISN approach and the ray-tracing approach are implemented in a computer code, SENSPG. The next section of this report presents the equations of the 1st- and 2nd-LASS for uncollided particles and the first- and second-order sensitivities that use the solutions of the 1st- and 2nd-LASS. Section III presents solutions of the 1st- and 2nd-LASS equations for the case of ray-tracing from a detector point. Section IV presents specific solutions of the 2nd-LASS and derives the ray-trace form of the inner products needed for second-order sensitivities. Numerical results for the total leakage from a homogeneous sphere are presented in Sec. V and for the leakage from one side of a two-region slab in Sec. VI. Section VII is a summary and conclusions.« less

NVIDIA OptiX ray-tracing engine as a new tool for modelling medical imaging systems

NASA Astrophysics Data System (ADS)

Pietrzak, Jakub; Kacperski, Krzysztof; Cieślar, Marek

2015-03-01

The most accurate technique to model the X- and gamma radiation path through a numerically defined object is the Monte Carlo simulation which follows single photons according to their interaction probabilities. A simplified and much faster approach, which just integrates total interaction probabilities along selected paths, is known as ray tracing. Both techniques are used in medical imaging for simulating real imaging systems and as projectors required in iterative tomographic reconstruction algorithms. These approaches are ready for massive parallel implementation e.g. on Graphics Processing Units (GPU), which can greatly accelerate the computation time at a relatively low cost. In this paper we describe the application of the NVIDIA OptiX ray-tracing engine, popular in professional graphics and rendering applications, as a new powerful tool for X- and gamma ray-tracing in medical imaging. It allows the implementation of a variety of physical interactions of rays with pixel-, mesh- or nurbs-based objects, and recording any required quantities, like path integrals, interaction sites, deposited energies, and others. Using the OptiX engine we have implemented a code for rapid Monte Carlo simulations of Single Photon Emission Computed Tomography (SPECT) imaging, as well as the ray-tracing projector, which can be used in reconstruction algorithms. The engine generates efficient, scalable and optimized GPU code, ready to run on multi GPU heterogeneous systems. We have compared the results our simulations with the GATE package. With the OptiX engine the computation time of a Monte Carlo simulation can be reduced from days to minutes.

140 GHz EC waves propagation and absorption for normal/oblique injection on FTU tokamak

NASA Astrophysics Data System (ADS)

Nowak, S.; Airoldi, A.; Bruschi, A.; Buratti, P.; Cirant, S.; Gandini, F.; Granucci, G.; Lazzaro, E.; Panaccione, L.; Ramponi, G.; Simonetto, A.; Sozzi, C.; Tudisco, O.; Zerbini, M.

1999-09-01

Most of the interest in ECRH experiments is linked to the high localization of EC waves absorption in well known portions of the plasma volume. In order to take full advantage of this capability a reliable code has been developed for beam tracing and absorption calculations. The code is particularly important for oblique (poloidal and toroidal) injection, when the absorbing layer is not simply dependent on the position of the EC resonance only. An experimental estimate of the local heating power density is given by the jump in the time derivative of the local electron pressure at the switching ON of the gyrotron power. The evolution of the temperature profile increase (from ECE polychromator) during the nearly adiabatic phase is also considered for ECRH profile reconstruction. An indirect estimate of optical thickness and of the overall absorption coefficient is given by the measure of the residual e.m. power at the tokamak walls. Beam tracing code predictions of the power deposition profile are compared with experimental estimates. The impact of the finite spatial resolution of the temperature diagnostic on profile reconstruction is also discussed.

Full wave simulations of helicon wave losses in the scrape-off-layer of the DIII-D tokamak

NASA Astrophysics Data System (ADS)

Lau, Cornwall; Jaeger, Fred; Berry, Lee; Bertelli, Nicola; Pinsker, Robert

2017-10-01

Helicon waves have been recently proposed as an off-axis current drive actuator for DIII-D. Previous modeling using the hot plasma, full wave code AORSA, has shown good agreement with the ray tracing code GENRAY for helicon wave propagation and absorption in the core plasma. AORSA, and a new, reduced finite-element-model show discrepancies between ray tracing and full wave occur in the scrape-off-layer (SOL), especially at high densities. The reduced model is much faster than AORSA, and reproduces most of the important features of the AORSA model. The reduced model also allows for larger parametric scans and for the easy use of arbitrary tokamak geometry. Results of the full wave codes, AORSA and COMSOL, will be shown for helicon wave losses in the SOL are shown for a large range of parameters, such as SOL density profiles, n||, radial and vertical locations of the antenna, and different tokamak vessel geometries. This work was supported by DE-AC05-00OR22725, DE-AC02-09CH11466, and DE-FC02-04ER54698.

Computational models for the analysis of three-dimensional internal and exhaust plume flowfields

NASA Technical Reports Server (NTRS)

Dash, S. M.; Delguidice, P. D.

1977-01-01

This paper describes computational procedures developed for the analysis of three-dimensional supersonic ducted flows and multinozzle exhaust plume flowfields. The models/codes embodying these procedures cater to a broad spectrum of geometric situations via the use of multiple reference plane grid networks in several coordinate systems. Shock capturing techniques are employed to trace the propagation and interaction of multiple shock surfaces while the plume interface, separating the exhaust and external flows, and the plume external shock are discretely analyzed. The computational grid within the reference planes follows the trace of streamlines to facilitate the incorporation of finite-rate chemistry and viscous computational capabilities. Exhaust gas properties consist of combustion products in chemical equilibrium. The computational accuracy of the models/codes is assessed via comparisons with exact solutions, results of other codes and experimental data. Results are presented for the flows in two-dimensional convergent and divergent ducts, expansive and compressive corner flows, flow in a rectangular nozzle and the plume flowfields for exhausts issuing out of single and multiple rectangular nozzles.

Economic evaluation of Cardio inCode®, a clinical-genetic function for coronary heart disease risk assessment.

PubMed

Ramírez de Arellano, A; Coca, A; de la Figuera, M; Rubio-Terrés, C; Rubio-Rodríguez, D; Gracia, A; Boldeanu, A; Puig-Gilberte, J; Salas, E

2013-10-01

A clinical–genetic function (Cardio inCode®) was generated using genetic variants associated with coronary heart disease (CHD), but not with classical CHD risk factors, to achieve a more precise estimation of the CHD risk of individuals by incorporating genetics into risk equations [Framingham and REGICOR (Registre Gironí del Cor)]. The objective of this study was to conduct an economic analysis of the CHD risk assessment with Cardio inCode®, which incorporates the patient’s genetic risk into the functions of REGICOR and Framingham, compared with the standard method (using only the functions). A Markov model was developed with seven states of health (low CHD risk, moderate CHD risk, high CHD risk, CHD event, recurrent CHD, chronic CHD, and death). The reclassification of CHD risk derived from genetic information and transition probabilities between states was obtained from a validation study conducted in cohorts of REGICOR (Spain) and Framingham (USA). It was assumed that patients classified as at moderate risk by the standard method were the best candidates to test the risk reclassification with Cardio inCode®. The utilities and costs (€; year 2011 values) of Markov states were obtained from the literature and Spanish sources. The analysis was performed from the perspective of the Spanish National Health System, for a life expectancy of 82 years in Spain. An annual discount rate of 3.5 % for costs and benefits was applied. For a Cardio inCode® price of €400, the cost per QALY gained compared with the standard method [incremental cost-effectiveness ratio (ICER)] would be €12,969 and €21,385 in REGICOR and Framingham cohorts, respectively. The threshold price of Cardio inCode® to reach the ICER threshold generally accepted in Spain (€30,000/QALY) would range between €668 and €836. The greatest benefit occurred in the subgroup of patients with moderate–high risk, with a high-risk reclassification of 22.8 % and 12 % of patients and an ICER of €1,652/QALY and €5,884/QALY in the REGICOR and Framingham cohorts, respectively. Sensitivity analyses confirmed the stability of the study results. Cardio inCode® is a cost-effective risk score option in CHD risk assessment compared with the standard method.

GRay: A MASSIVELY PARALLEL GPU-BASED CODE FOR RAY TRACING IN RELATIVISTIC SPACETIMES

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

Chan, Chi-kwan; Psaltis, Dimitrios; Özel, Feryal

We introduce GRay, a massively parallel integrator designed to trace the trajectories of billions of photons in a curved spacetime. This graphics-processing-unit (GPU)-based integrator employs the stream processing paradigm, is implemented in CUDA C/C++, and runs on nVidia graphics cards. The peak performance of GRay using single-precision floating-point arithmetic on a single GPU exceeds 300 GFLOP (or 1 ns per photon per time step). For a realistic problem, where the peak performance cannot be reached, GRay is two orders of magnitude faster than existing central-processing-unit-based ray-tracing codes. This performance enhancement allows more effective searches of large parameter spaces when comparingmore » theoretical predictions of images, spectra, and light curves from the vicinities of compact objects to observations. GRay can also perform on-the-fly ray tracing within general relativistic magnetohydrodynamic algorithms that simulate accretion flows around compact objects. Making use of this algorithm, we calculate the properties of the shadows of Kerr black holes and the photon rings that surround them. We also provide accurate fitting formulae of their dependencies on black hole spin and observer inclination, which can be used to interpret upcoming observations of the black holes at the center of the Milky Way, as well as M87, with the Event Horizon Telescope.« less

TransFit: Finite element analysis data fitting software

NASA Technical Reports Server (NTRS)

Freeman, Mark

1993-01-01

The Advanced X-Ray Astrophysics Facility (AXAF) mission support team has made extensive use of geometric ray tracing to analyze the performance of AXAF developmental and flight optics. One important aspect of this performance modeling is the incorporation of finite element analysis (FEA) data into the surface deformations of the optical elements. TransFit is software designed for the fitting of FEA data of Wolter I optical surface distortions with a continuous surface description which can then be used by SAO's analytic ray tracing software, currently OSAC (Optical Surface Analysis Code). The improved capabilities of Transfit over previous methods include bicubic spline fitting of FEA data to accommodate higher spatial frequency distortions, fitted data visualization for assessing the quality of fit, the ability to accommodate input data from three FEA codes plus other standard formats, and options for alignment of the model coordinate system with the ray trace coordinate system. TransFit uses the AnswerGarden graphical user interface (GUI) to edit input parameters and then access routines written in PV-WAVE, C, and FORTRAN to allow the user to interactively create, evaluate, and modify the fit. The topics covered include an introduction to TransFit: requirements, designs philosophy, and implementation; design specifics: modules, parameters, fitting algorithms, and data displays; a procedural example; verification of performance; future work; and appendices on online help and ray trace results of the verification section.

Genetic Programming-based Phononic Bandgap Structure Design

DTIC Science & Technology

2011-09-01

derivative-based methods is that they require a good starting location to find the global minimum of a function. As can be seen from figure 2, there are many... FRANCHI CODE 7100 M H ORR CODE 7120 J A BUCARO CODE 7130 G J ORRIS 7140 J S PERKINS CODE 7140 S A CHIN BING CODE 7180 4555 OVERLOOK AVE SW WASHINGTON DC

Inter-individual variation in expression: a missing link in biomarker biology?

PubMed

Little, Peter F R; Williams, Rohan B H; Wilkins, Marc R

2009-01-01

The past decade has seen an explosion of variation data demonstrating that diversity of both protein-coding sequences and of regulatory elements of protein-coding genes is common and of functional importance. In this article, we argue that genetic diversity can no longer be ignored in studies of human biology, even research projects without explicit genetic experimental design, and that this knowledge can, and must, inform research. By way of illustration, we focus on the potential role of genetic data in case-control studies to identify and validate cancer protein biomarkers. We argue that a consideration of genetics, in conjunction with proteomic biomarker discovery projects, should improve the proportion of biomarkers that can accurately classify patients.

More Than Bar Codes: Integrating Global Standards-Based Bar Code Technology Into National Health Information Systems in Ethiopia and Pakistan to Increase End-to-End Supply Chain Visibility.

PubMed

Hara, Liuichi; Guirguis, Ramy; Hummel, Keith; Villanueva, Monica

2017-12-28

The United Nations Population Fund (UNFPA) and the United States Agency for International Development (USAID) DELIVER PROJECT work together to strengthen public health commodity supply chains by standardizing bar coding under a single set of global standards. From 2015, UNFPA and USAID collaborated to pilot test how tracking and tracing of bar coded health products could be operationalized in the public health supply chains of Ethiopia and Pakistan and inform the ecosystem needed to begin full implementation. Pakistan had been using proprietary bar codes for inventory management of contraceptive supplies but transitioned to global standards-based bar codes during the pilot. The transition allowed Pakistan to leverage the original bar codes that were preprinted by global manufacturers as opposed to printing new bar codes at the central warehouse. However, barriers at lower service delivery levels prevented full realization of end-to-end data visibility. Key barriers at the district level were the lack of a digital inventory management system and absence of bar codes at the primary-level packaging level, such as single blister packs. The team in Ethiopia developed an open-sourced smartphone application that allowed the team to scan bar codes using the mobile phone's camera and to push the captured data to the country's data mart. Real-time tracking and tracing occurred from the central warehouse to the Addis Ababa distribution hub and to 2 health centers. These pilots demonstrated that standardized product identification and bar codes can significantly improve accuracy over manual stock counts while significantly streamlining the stock-taking process, resulting in efficiencies. The pilots also showed that bar coding technology by itself is not sufficient to ensure data visibility. Rather, by using global standards for identification and data capture of pharmaceuticals and medical devices, and integrating the data captured into national and global tracking systems, countries are able to lay the foundation for interoperability and ensure a harmonized language between global health stakeholders. © Hara et al.

More Than Bar Codes: Integrating Global Standards-Based Bar Code Technology Into National Health Information Systems in Ethiopia and Pakistan to Increase End-to-End Supply Chain Visibility

PubMed Central

Hara, Liuichi; Guirguis, Ramy; Hummel, Keith; Villanueva, Monica

2017-01-01

The United Nations Population Fund (UNFPA) and the United States Agency for International Development (USAID) DELIVER PROJECT work together to strengthen public health commodity supply chains by standardizing bar coding under a single set of global standards. From 2015, UNFPA and USAID collaborated to pilot test how tracking and tracing of bar coded health products could be operationalized in the public health supply chains of Ethiopia and Pakistan and inform the ecosystem needed to begin full implementation. Pakistan had been using proprietary bar codes for inventory management of contraceptive supplies but transitioned to global standards-based bar codes during the pilot. The transition allowed Pakistan to leverage the original bar codes that were preprinted by global manufacturers as opposed to printing new bar codes at the central warehouse. However, barriers at lower service delivery levels prevented full realization of end-to-end data visibility. Key barriers at the district level were the lack of a digital inventory management system and absence of bar codes at the primary-level packaging level, such as single blister packs. The team in Ethiopia developed an open-sourced smartphone application that allowed the team to scan bar codes using the mobile phone's camera and to push the captured data to the country's data mart. Real-time tracking and tracing occurred from the central warehouse to the Addis Ababa distribution hub and to 2 health centers. These pilots demonstrated that standardized product identification and bar codes can significantly improve accuracy over manual stock counts while significantly streamlining the stock-taking process, resulting in efficiencies. The pilots also showed that bar coding technology by itself is not sufficient to ensure data visibility. Rather, by using global standards for identification and data capture of pharmaceuticals and medical devices, and integrating the data captured into national and global tracking systems, countries are able to lay the foundation for interoperability and ensure a harmonized language between global health stakeholders. PMID:29284701

Trace element abundances in major minerals of Late Permian coals from southwestern Guizhou province, China

USGS Publications Warehouse

Zhang, Jiahua; Ren, D.; Zheng, C.; Zeng, R.; Chou, C.-L.; Liu, J.

2002-01-01

Fourteen samples of minerals were separated by handpicking from Late Permian coals in southwestern Guizhou province, China. These 14 minerals were nodular pyrite, massive recrystallized pyrite, pyrite deposited from low-temperature hydrothermal fluid and from ground water; clay minerals; and calcite deposited from low-temperature hydrothermal fluid and from ground water. The mineralogy, elemental composition, and distribution of 33 elements in these samples were studied by optical microscopy, scanning electron microscope equipped with energy-dispersive X-ray spectrometer (SEM-EDX), X-ray diffraction (XRD), cold-vapor atomic absorption spectrometry (CV-AAS), atomic fluorescence spectrometry (AFS), inductively coupled-plasma mass spectrometry (ICP-MS), and ion-selective electrode (ISE). The results show that various minerals in coal contain variable amounts of trace elements. Clay minerals have high concentrations of Ba, Be, Cs, F, Ga, Nb, Rb, Th, U, and Zr. Quartz has little contribution to the concentration of trace elements in bulk coal. Arsenic, Mn, and Sr are in high concentrations in calcite. Pyrite has high concentrations of As, Cd, Hg, Mo, Sb, Se, Tl, and Zn. Different genetic types of calcite in coal can accumulate different trace elements; for example Ba, Co, Cr, Hg, Ni, Rb, Sn, Sr, and Zn are in higher concentrations in calcite deposited from low-temperature hydrothermal fluid than in that deposited from ground water. Furthermore, the concentrations of some trace elements are quite variable in pyrite; different genetic types of pyrites (Py-A, B, C, D) have different concentrations of trace elements, and the concentrations of trace elements are also different in pyrite of low-temperature hydrothermal origin collected from different locations. The study shows that elemental concentration is rather uniform in a pyrite vein. There are many micron and submicron mosaic pyrites in a pyrite vein, which is enriched in some trace elements, such as As and Mo. The content of trace element in pyrite vein depends upon the content of mosaic pyrite and of trace elements in it. Many environmentally sensitive trace elements are mainly contained in the minerals in coal, and hence the physical coal cleaning techniques can remove minerals from coal and decrease the emissions of potentially hazardous trace elements. ?? 2002 Elsevier Science B.V. All rights reserved.

A SNP panel and online tool for checking genotype concordance through comparing QR codes.

PubMed

Du, Yonghong; Martin, Joshua S; McGee, John; Yang, Yuchen; Liu, Eric Yi; Sun, Yingrui; Geihs, Matthias; Kong, Xuejun; Zhou, Eric Lingfeng; Li, Yun; Huang, Jie

2017-01-01

In the current precision medicine era, more and more samples get genotyped and sequenced. Both researchers and commercial companies expend significant time and resources to reduce the error rate. However, it has been reported that there is a sample mix-up rate of between 0.1% and 1%, not to mention the possibly higher mix-up rate during the down-stream genetic reporting processes. Even on the low end of this estimate, this translates to a significant number of mislabeled samples, especially over the projected one billion people that will be sequenced within the next decade. Here, we first describe a method to identify a small set of Single nucleotide polymorphisms (SNPs) that can uniquely identify a personal genome, which utilizes allele frequencies of five major continental populations reported in the 1000 genomes project and the ExAC Consortium. To make this panel more informative, we added four SNPs that are commonly used to predict ABO blood type, and another two SNPs that are capable of predicting sex. We then implement a web interface (http://qrcme.tech), nicknamed QRC (for QR code based Concordance check), which is capable of extracting the relevant ID SNPs from a raw genetic data, coding its genotype as a quick response (QR) code, and comparing QR codes to report the concordance of underlying genetic datasets. The resulting 80 fingerprinting SNPs represent a significant decrease in complexity and the number of markers used for genetic data labelling and tracking. Our method and web tool is easily accessible to both researchers and the general public who consider the accuracy of complex genetic data as a prerequisite towards precision medicine.

A SNP panel and online tool for checking genotype concordance through comparing QR codes

PubMed Central

Du, Yonghong; Martin, Joshua S.; McGee, John; Yang, Yuchen; Liu, Eric Yi; Sun, Yingrui; Geihs, Matthias; Kong, Xuejun; Zhou, Eric Lingfeng; Li, Yun

2017-01-01

In the current precision medicine era, more and more samples get genotyped and sequenced. Both researchers and commercial companies expend significant time and resources to reduce the error rate. However, it has been reported that there is a sample mix-up rate of between 0.1% and 1%, not to mention the possibly higher mix-up rate during the down-stream genetic reporting processes. Even on the low end of this estimate, this translates to a significant number of mislabeled samples, especially over the projected one billion people that will be sequenced within the next decade. Here, we first describe a method to identify a small set of Single nucleotide polymorphisms (SNPs) that can uniquely identify a personal genome, which utilizes allele frequencies of five major continental populations reported in the 1000 genomes project and the ExAC Consortium. To make this panel more informative, we added four SNPs that are commonly used to predict ABO blood type, and another two SNPs that are capable of predicting sex. We then implement a web interface (http://qrcme.tech), nicknamed QRC (for QR code based Concordance check), which is capable of extracting the relevant ID SNPs from a raw genetic data, coding its genotype as a quick response (QR) code, and comparing QR codes to report the concordance of underlying genetic datasets. The resulting 80 fingerprinting SNPs represent a significant decrease in complexity and the number of markers used for genetic data labelling and tracking. Our method and web tool is easily accessible to both researchers and the general public who consider the accuracy of complex genetic data as a prerequisite towards precision medicine. PMID:28926565

Interdependence, Reflexivity, Fidelity, Impedance Matching, and the Evolution of Genetic Coding

PubMed Central

Carter, Charles W; Wills, Peter R

2018-01-01

Abstract Genetic coding is generally thought to have required ribozymes whose functions were taken over by polypeptide aminoacyl-tRNA synthetases (aaRS). Two discoveries about aaRS and their interactions with tRNA substrates now furnish a unifying rationale for the opposite conclusion: that the key processes of the Central Dogma of molecular biology emerged simultaneously and naturally from simple origins in a peptide•RNA partnership, eliminating the epistemological utility of a prior RNA world. First, the two aaRS classes likely arose from opposite strands of the same ancestral gene, implying a simple genetic alphabet. The resulting inversion symmetries in aaRS structural biology would have stabilized the initial and subsequent differentiation of coding specificities, rapidly promoting diversity in the proteome. Second, amino acid physical chemistry maps onto tRNA identity elements, establishing reflexive, nanoenvironmental sensing in protein aaRS. Bootstrapping of increasingly detailed coding is thus intrinsic to polypeptide aaRS, but impossible in an RNA world. These notions underline the following concepts that contradict gradual replacement of ribozymal aaRS by polypeptide aaRS: 1) aaRS enzymes must be interdependent; 2) reflexivity intrinsic to polypeptide aaRS production dynamics promotes bootstrapping; 3) takeover of RNA-catalyzed aminoacylation by enzymes will necessarily degrade specificity; and 4) the Central Dogma’s emergence is most probable when replication and translation error rates remain comparable. These characteristics are necessary and sufficient for the essentially de novo emergence of a coupled gene–replicase–translatase system of genetic coding that would have continuously preserved the functional meaning of genetically encoded protein genes whose phylogenetic relationships match those observed today. PMID:29077934

Genomic Editing of Non-Coding RNA Genes with CRISPR/Cas9 Ushers in a Potential Novel Approach to Study and Treat Schizophrenia

PubMed Central

Zhuo, Chuanjun; Hou, Weihong; Hu, Lirong; Lin, Chongguang; Chen, Ce; Lin, Xiaodong

2017-01-01

Schizophrenia is a genetically related mental illness, in which the majority of genetic alterations occur in the non-coding regions of the human genome. In the past decade, a growing number of regulatory non-coding RNAs (ncRNAs) including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been identified to be strongly associated with schizophrenia. However, the studies of these ncRNAs in the pathophysiology of schizophrenia and the reverting of their genetic defects in restoration of the normal phenotype have been hampered by insufficient technology to manipulate these ncRNA genes effectively as well as a lack of appropriate animal models. Most recently, a revolutionary gene editing technology known as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9; CRISPR/Cas9) has been developed that enable researchers to overcome these challenges. In this review article, we mainly focus on the schizophrenia-related ncRNAs and the use of CRISPR/Cas9-mediated editing on the non-coding regions of the genomic DNA in proving causal relationship between the genetic defects and the pathophysiology of schizophrenia. We subsequently discuss the potential of translating this advanced technology into a clinical therapy for schizophrenia, although the CRISPR/Cas9 technology is currently still in its infancy and immature to put into use in the treatment of diseases. Furthermore, we suggest strategies to accelerate the pace from the bench to the bedside. This review describes the application of the powerful and feasible CRISPR/Cas9 technology to manipulate schizophrenia-associated ncRNA genes. This technology could help researchers tackle this complex health problem and perhaps other genetically related mental disorders due to the overlapping genetic alterations of schizophrenia with other mental illnesses. PMID:28217082

Adult stem cell lineage tracing and deep tissue imaging

PubMed Central

Fink, Juergen; Andersson-Rolf, Amanda; Koo, Bon-Kyoung

2015-01-01

Lineage tracing is a widely used method for understanding cellular dynamics in multicellular organisms during processes such as development, adult tissue maintenance, injury repair and tumorigenesis. Advances in tracing or tracking methods, from light microscopy-based live cell tracking to fluorescent label-tracing with two-photon microscopy, together with emerging tissue clearing strategies and intravital imaging approaches have enabled scientists to decipher adult stem and progenitor cell properties in various tissues and in a wide variety of biological processes. Although technical advances have enabled time-controlled genetic labeling and simultaneous live imaging, a number of obstacles still need to be overcome. In this review, we aim to provide an in-depth description of the traditional use of lineage tracing as well as current strategies and upcoming new methods of labeling and imaging. [BMB Reports 2015; 48(12): 655-667] PMID:26634741

A novel nuclear genetic code alteration in yeasts and the evolution of codon reassignment in eukaryotes

PubMed Central

Mühlhausen, Stefanie; Findeisen, Peggy; Plessmann, Uwe; Urlaub, Henning; Kollmar, Martin

2016-01-01

The genetic code is the cellular translation table for the conversion of nucleotide sequences into amino acid sequences. Changes to the meaning of sense codons would introduce errors into almost every translated message and are expected to be highly detrimental. However, reassignment of single or multiple codons in mitochondria and nuclear genomes, although extremely rare, demonstrates that the code can evolve. Several models for the mechanism of alteration of nuclear genetic codes have been proposed (including “codon capture,” “genome streamlining,” and “ambiguous intermediate” theories), but with little resolution. Here, we report a novel sense codon reassignment in Pachysolen tannophilus, a yeast related to the Pichiaceae. By generating proteomics data and using tRNA sequence comparisons, we show that Pachysolen translates CUG codons as alanine and not as the more usual leucine. The Pachysolen tRNACAG is an anticodon-mutated tRNAAla containing all major alanine tRNA recognition sites. The polyphyly of the CUG-decoding tRNAs in yeasts is best explained by a tRNA loss driven codon reassignment mechanism. Loss of the CUG-tRNA in the ancient yeast is followed by gradual decrease of respective codons and subsequent codon capture by tRNAs whose anticodon is not part of the aminoacyl-tRNA synthetase recognition region. Our hypothesis applies to all nuclear genetic code alterations and provides several testable predictions. We anticipate more codon reassignments to be uncovered in existing and upcoming genome projects. PMID:27197221

TIP: protein backtranslation aided by genetic algorithms.

PubMed

Moreira, Andrés; Maass, Alejandro

2004-09-01

Several applications require the backtranslation of a protein sequence into a nucleic acid sequence. The degeneracy of the genetic code makes this process ambiguous; moreover, not every translation is equally viable. The usual answer is to mimic the codon usage of the target species; however, this does not capture all the relevant features of the 'genomic styles' from different taxa. The program TIP ' Traducción Inversa de Proteínas') applies genetic algorithms to improve the backtranslation, by minimizing the difference of some coding statistics with respect to their average value in the target. http://www.cmm.uchile.cl/genoma/tip/

Expanding and reprogramming the genetic code.

PubMed

Chin, Jason W

2017-10-04

Nature uses a limited, conservative set of amino acids to synthesize proteins. The ability to genetically encode an expanded set of building blocks with new chemical and physical properties is transforming the study, manipulation and evolution of proteins, and is enabling diverse applications, including approaches to probe, image and control protein function, and to precisely engineer therapeutics. Underpinning this transformation are strategies to engineer and rewire translation. Emerging strategies aim to reprogram the genetic code so that noncanonical biopolymers can be synthesized and evolved, and to test the limits of our ability to engineer the translational machinery and systematically recode genomes.

Simulations of Laboratory Astrophysics Experiments using the CRASH code

NASA Astrophysics Data System (ADS)

Trantham, Matthew; Kuranz, Carolyn; Fein, Jeff; Wan, Willow; Young, Rachel; Keiter, Paul; Drake, R. Paul

2015-11-01

Computer simulations can assist in the design and analysis of laboratory astrophysics experiments. The Center for Radiative Shock Hydrodynamics (CRASH) at the University of Michigan developed a code that has been used to design and analyze high-energy-density experiments on OMEGA, NIF, and other large laser facilities. This Eulerian code uses block-adaptive mesh refinement (AMR) with implicit multigroup radiation transport, electron heat conduction and laser ray tracing. This poster will demonstrate some of the experiments the CRASH code has helped design or analyze including: Kelvin-Helmholtz, Rayleigh-Taylor, magnetized flows, jets, and laser-produced plasmas. This work is funded by the following grants: DEFC52-08NA28616, DE-NA0001840, and DE-NA0002032.

The Genetic Privacy Act and commentary

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

Annas, G.J.; Glantz, L.H.; Roche, P.A.

1995-02-28

The Genetic Privacy Act is a proposal for federal legislation. The Act is based on the premise that genetic information is different from other types of personal information in ways that require special protection. The DNA molecule holds an extensive amount of currently indecipherable information. The major goal of the Human Genome Project is to decipher this code so that the information it contains is accessible. The privacy question is, accessible to whom? The highly personal nature of the information contained in DNA can be illustrated by thinking of DNA as containing an individual`s {open_quotes}future diary.{close_quotes} A diary is perhapsmore » the most personal and private document a person can create. It contains a person`s innermost thoughts and perceptions, and is usually hidden and locked to assure its secrecy. Diaries describe the past. The information in one`s genetic code can be thought of as a coded probabilistic future diary because it describes an important part of a unique and personal future. This document presents an introduction to the proposal for federal legislation `the Genetic Privacy Act`; a copy of the proposed act; and comment.« less

Tracing Multiple Generations of Active Galactic Nucleau Feedback in the Core of Abell 262

DTIC Science & Technology

2009-06-01

Virgo cluster reveal a series of filaments, which trace regions that are thought 1481 Report Documentation Page Form ApprovedOMB No. 0704-0188 Public...L. Sarazin4, L. D. Anderson3, Gopal-Krishna5, E. M. Douglass3, and N. E. Kassim1 1 Naval Research Laboratory, 4555 Overlook Avenue SW, Code 7213...Washington, DC 20375, USA 2 Interferometrics Inc., 13454 Sunrise Valley Drive, Suite 240, Herndon, VA 20171, USA 3 Institute for Astrophysical Research

The SNPforID Assay as a Supplementary Method in Kinship and Trace Analysis

PubMed Central

Schwark, Thorsten; Meyer, Patrick; Harder, Melanie; Modrow, Jan-Hendrick; von Wurmb-Schwark, Nicole

2012-01-01

Objective Short tandem repeat (STR) analysis using commercial multiplex PCR kits is the method of choice for kinship testing and trace analysis. However, under certain circumstances (deficiency testing, mutations, minute DNA amounts), STRs alone may not suffice. Methods We present a 50-plex single nucleotide polymorphism (SNP) assay based on the SNPs chosen by the SNPforID consortium as an additional method for paternity and for trace analysis. The new assay was applied to selected routine paternity and trace cases from our laboratory. Results and Conclusions Our investigation shows that the new SNP multiplex assay is a valuable method to supplement STR analysis, and is a powerful means to solve complicated genetic analyses. PMID:22851934

Signal-processing theory for the TurboRogue receiver

NASA Technical Reports Server (NTRS)

Thomas, J. B.

1995-01-01

Signal-processing theory for the TurboRogue receiver is presented. The signal form is traced from its formation at the GPS satellite, to the receiver antenna, and then through the various stages of the receiver, including extraction of phase and delay. The analysis treats the effects of ionosphere, troposphere, signal quantization, receiver components, and system noise, covering processing in both the 'code mode' when the P code is not encrypted and in the 'P-codeless mode' when the P code is encrypted. As a possible future improvement to the current analog front end, an example of a highly digital front end is analyzed.

Cells of Origin of Epithelial Ovarian Cancers

DTIC Science & Technology

2015-09-01

cells in oral squamous cell carcinomas by a novel pathway-based lineage tracing approach in a murine model. ! 13! Specific aims: 1. Determine...SUNDARESAN Lineage tracing and clonal analysis of oral cancer initiating cells The goal of this project is to study cancer stem cells /cancer initiating...whether oral cancer cells genetically marked based on their activities for stem cell -related pathways exhibit cancer stem cell properties in vivo by

Reading the Second Code: Mapping Epigenomes to Understand Plant Growth, Development, and Adaptation to the Environment[OA

PubMed Central

2012-01-01

We have entered a new era in agricultural and biomedical science made possible by remarkable advances in DNA sequencing technologies. The complete sequence of an individual’s set of chromosomes (collectively, its genome) provides a primary genetic code for what makes that individual unique, just as the contents of every personal computer reflect the unique attributes of its owner. But a second code, composed of “epigenetic” layers of information, affects the accessibility of the stored information and the execution of specific tasks. Nature’s second code is enigmatic and must be deciphered if we are to fully understand and optimize the genetic potential of crop plants. The goal of the Epigenomics of Plants International Consortium is to crack this second code, and ultimately master its control, to help catalyze a new green revolution. PMID:22751210

PCR-free quantitative detection of genetically modified organism from raw materials. An electrochemiluminescence-based bio bar code method.

PubMed

Zhu, Debin; Tang, Yabing; Xing, Da; Chen, Wei R

2008-05-15

A bio bar code assay based on oligonucleotide-modified gold nanoparticles (Au-NPs) provides a PCR-free method for quantitative detection of nucleic acid targets. However, the current bio bar code assay requires lengthy experimental procedures including the preparation and release of bar code DNA probes from the target-nanoparticle complex and immobilization and hybridization of the probes for quantification. Herein, we report a novel PCR-free electrochemiluminescence (ECL)-based bio bar code assay for the quantitative detection of genetically modified organism (GMO) from raw materials. It consists of tris-(2,2'-bipyridyl) ruthenium (TBR)-labeled bar code DNA, nucleic acid hybridization using Au-NPs and biotin-labeled probes, and selective capture of the hybridization complex by streptavidin-coated paramagnetic beads. The detection of target DNA is realized by direct measurement of ECL emission of TBR. It can quantitatively detect target nucleic acids with high speed and sensitivity. This method can be used to quantitatively detect GMO fragments from real GMO products.

A unified model of the standard genetic code.

PubMed

José, Marco V; Zamudio, Gabriel S; Morgado, Eberto R

2017-03-01

The Rodin-Ohno (RO) and the Delarue models divide the table of the genetic code into two classes of aminoacyl-tRNA synthetases (aaRSs I and II) with recognition from the minor or major groove sides of the tRNA acceptor stem, respectively. These models are asymmetric but they are biologically meaningful. On the other hand, the standard genetic code (SGC) can be derived from the primeval RNY code (R stands for purines, Y for pyrimidines and N any of them). In this work, the RO-model is derived by means of group actions, namely, symmetries represented by automorphisms, assuming that the SGC originated from a primeval RNY code. It turns out that the RO-model is symmetric in a six-dimensional (6D) hypercube. Conversely, using the same automorphisms, we show that the RO-model can lead to the SGC. In addition, the asymmetric Delarue model becomes symmetric by means of quotient group operations. We formulate isometric functions that convert the class aaRS I into the class aaRS II and vice versa. We show that the four polar requirement categories display a symmetrical arrangement in our 6D hypercube. Altogether these results cannot be attained, neither in two nor in three dimensions. We discuss the present unified 6D algebraic model, which is compatible with both the SGC (based upon the primeval RNY code) and the RO-model.

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

Vassilevska, Tanya

This is the first code, designed to run on a desktop, which models the intracellular replication and the cell-to-cell infection and demonstrates virus evolution at the molecular level. This code simulates the infection of a population of "idealized biological cells" (represented as objects that do not divide or have metabolism) with "virus" (represented by its genetic sequence), the replication and simultaneous mutation of the virus which leads to evolution of the population of genetically diverse viruses. The code is built to simulate single-stranded RNA viruses. The input for the code is 1. the number of biological cells in the culture,more » 2. the initial composition of the virus population, 3. the reference genome of the RNA virus, 4. the coordinates of the genome regions and their significance and, 5. parameters determining the dynamics of virus replication, such as the mutation rate. The simulation ends when all cells have been infected or when no more infections occurs after a given number of attempts. The code has the ability to simulate the evolution of the virus in serial passage of cell "cultures", i.e. after the end of a simulation, a new one is immediately scheduled with a new culture of infected cells. The code outputs characteristics of the resulting virus population dynamics and genetic composition of the virus population, such as the top dominant genomes, percentage of a genome with specific characteristics.« less

The "Wow! signal" of the terrestrial genetic code

NASA Astrophysics Data System (ADS)

shCherbak, Vladimir I.; Makukov, Maxim A.

2013-05-01

It has been repeatedly proposed to expand the scope for SETI, and one of the suggested alternatives to radio is the biological media. Genomic DNA is already used on Earth to store non-biological information. Though smaller in capacity, but stronger in noise immunity is the genetic code. The code is a flexible mapping between codons and amino acids, and this flexibility allows modifying the code artificially. But once fixed, the code might stay unchanged over cosmological timescales; in fact, it is the most durable construct known. Therefore it represents an exceptionally reliable storage for an intelligent signature, if that conforms to biological and thermodynamic requirements. As the actual scenario for the origin of terrestrial life is far from being settled, the proposal that it might have been seeded intentionally cannot be ruled out. A statistically strong intelligent-like "signal" in the genetic code is then a testable consequence of such scenario. Here we show that the terrestrial code displays a thorough precision-type orderliness matching the criteria to be considered an informational signal. Simple arrangements of the code reveal an ensemble of arithmetical and ideographical patterns of the same symbolic language. Accurate and systematic, these underlying patterns appear as a product of precision logic and nontrivial computing rather than of stochastic processes (the null hypothesis that they are due to chance coupled with presumable evolutionary pathways is rejected with P-value < 10-13). The patterns are profound to the extent that the code mapping itself is uniquely deduced from their algebraic representation. The signal displays readily recognizable hallmarks of artificiality, among which are the symbol of zero, the privileged decimal syntax and semantical symmetries. Besides, extraction of the signal involves logically straightforward but abstract operations, making the patterns essentially irreducible to any natural origin. Plausible ways of embedding the signal into the code and possible interpretation of its content are discussed. Overall, while the code is nearly optimized biologically, its limited capacity is used extremely efficiently to pass non-biological information.

TIM, a ray-tracing program for METATOY research and its dissemination

NASA Astrophysics Data System (ADS)

Lambert, Dean; Hamilton, Alasdair C.; Constable, George; Snehanshu, Harsh; Talati, Sharvil; Courtial, Johannes

2012-03-01

TIM (The Interactive METATOY) is a ray-tracing program specifically tailored towards our research in METATOYs, which are optical components that appear to be able to create wave-optically forbidden light-ray fields. For this reason, TIM possesses features not found in other ray-tracing programs. TIM can either be used interactively or by modifying the openly available source code; in both cases, it can easily be run as an applet embedded in a web page. Here we describe the basic structure of TIM's source code and how to extend it, and we give examples of how we have used TIM in our own research. Program summaryProgram title: TIM Catalogue identifier: AEKY_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEKY_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public License No. of lines in distributed program, including test data, etc.: 124 478 No. of bytes in distributed program, including test data, etc.: 4 120 052 Distribution format: tar.gz Programming language: Java Computer: Any computer capable of running the Java Virtual Machine (JVM) 1.6 Operating system: Any; developed under Mac OS X Version 10.6 RAM: Typically 145 MB (interactive version running under Mac OS X Version 10.6) Classification: 14, 18 External routines: JAMA [1] (source code included) Nature of problem: Visualisation of scenes that include scene objects that create wave-optically forbidden light-ray fields. Solution method: Ray tracing. Unusual features: Specifically designed to visualise wave-optically forbidden light-ray fields; can visualise ray trajectories; can visualise geometric optic transformations; can create anaglyphs (for viewing with coloured "3D glasses") and random-dot autostereograms of the scene; integrable into web pages. Running time: Problem-dependent; typically seconds for a simple scene.

Introducing GAMER: A fast and accurate method for ray-tracing galaxies using procedural noise

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

Groeneboom, N. E.; Dahle, H., E-mail: nicolaag@astro.uio.no

2014-03-10

We developed a novel approach for fast and accurate ray-tracing of galaxies using procedural noise fields. Our method allows for efficient and realistic rendering of synthetic galaxy morphologies, where individual components such as the bulge, disk, stars, and dust can be synthesized in different wavelengths. These components follow empirically motivated overall intensity profiles but contain an additional procedural noise component that gives rise to complex natural patterns that mimic interstellar dust and star-forming regions. These patterns produce more realistic-looking galaxy images than using analytical expressions alone. The method is fully parallelized and creates accurate high- and low- resolution images thatmore » can be used, for example, in codes simulating strong and weak gravitational lensing. In addition to having a user-friendly graphical user interface, the C++ software package GAMER is easy to implement into an existing code.« less

Introducing GAMER: A Fast and Accurate Method for Ray-tracing Galaxies Using Procedural Noise

NASA Astrophysics Data System (ADS)

Groeneboom, N. E.; Dahle, H.

2014-03-01

We developed a novel approach for fast and accurate ray-tracing of galaxies using procedural noise fields. Our method allows for efficient and realistic rendering of synthetic galaxy morphologies, where individual components such as the bulge, disk, stars, and dust can be synthesized in different wavelengths. These components follow empirically motivated overall intensity profiles but contain an additional procedural noise component that gives rise to complex natural patterns that mimic interstellar dust and star-forming regions. These patterns produce more realistic-looking galaxy images than using analytical expressions alone. The method is fully parallelized and creates accurate high- and low- resolution images that can be used, for example, in codes simulating strong and weak gravitational lensing. In addition to having a user-friendly graphical user interface, the C++ software package GAMER is easy to implement into an existing code.

Presynaptic Inputs to Any CNS Projection Neuron Identified by Dual Recombinant Virus Infection

PubMed Central

Bráz, João M.; Wang, Fan; Basbaum, Allan I.

2015-01-01

Although neuroanatomical tracing studies have defined the origin and targets of major projection neurons (PN) of the central nervous system (CNS), there is much less information about the circuits that influence these neurons. Recently, genetic approaches that use Cre recombinase-dependent viral vectors have greatly facilitated such circuit analysis, but these tracing approaches are limited by the availability of Cre-expressing mouse lines and the difficulty in restricting Cre expression to discrete regions of the CNS. Here, we illustrate an alternative approach to drive Cre expression specifically in defined subsets of CNS projection neurons, so as to map both direct and indirect presynaptic inputs to these cells. The method involves a combination of Cre-dependent transneuronal viral tracers that can be used in the adult and that does not require genetically modified mice. To trigger Cre-expression we inject a Cre-expressing adenovirus that is retrogradely transported to the projection neurons of interest. The region containing the retrogradely labeled projection neurons is next injected with Cre-dependent pseudorabies or rabies vectors, which results in labeling of poly- and monosynaptic neuronal inputs, respectively. In proof-of-concept experiments, we used this novel tracing system to study the circuits that engage projection neurons of the superficial dorsal horn of the spinal cord and trigeminal nucleus caudalis, neurons of the parabrachial nucleus of the dorsolateral pons that project to the amygdala and cortically-projecting neurons of the lateral geniculate nucleus. Importantly, because this dual viral tracing method does not require genetically derived Cre-expressing mouse lines, inputs to almost any projection system can be studied and the analysis can be performed in larger animals, such as the rat. PMID:26470056

SETI in vivo: testing the we-are-them hypothesis

NASA Astrophysics Data System (ADS)

Makukov, Maxim A.; Shcherbak, Vladimir I.

2018-04-01

After it was proposed that life on Earth might descend from seeding by an earlier extraterrestrial civilization motivated to secure and spread life, some authors noted that this alternative offers a testable implication: microbial seeds could be intentionally supplied with a durable signature that might be found in extant organisms. In particular, it was suggested that the optimal location for such an artefact is the genetic code, as the least evolving part of cells. However, as the mainstream view goes, this scenario is too speculative and cannot be meaningfully tested because encoding/decoding a signature within the genetic code is something ill-defined, so any retrieval attempt is doomed to guesswork. Here we refresh the seeded-Earth hypothesis in light of recent observations, and discuss the motivation for inserting a signature. We then show that `biological SETI' involves even weaker assumptions than traditional SETI and admits a well-defined methodological framework. After assessing the possibility in terms of molecular and evolutionary biology, we formalize the approach and, adopting the standard guideline of SETI that encoding/decoding should follow from first principles and be convention-free, develop a universal retrieval strategy. Applied to the canonical genetic code, it reveals a non-trivial precision structure of interlocked logical and numerical attributes of systematic character (previously we found these heuristically). To assess this result in view of the initial assumption, we perform statistical, comparison, interdependence and semiotic analyses. Statistical analysis reveals no causal connection of the result to evolutionary models of the genetic code, interdependence analysis precludes overinterpretation, and comparison analysis shows that known variations of the code lack any precision-logic structures, in agreement with these variations being post-LUCA (i.e. post-seeding) evolutionary deviations from the canonical code. Finally, semiotic analysis shows that not only the found attributes are consistent with the initial assumption, but that they make perfect sense from SETI perspective, as they ultimately maintain some of the most universal codes of culture.

The chemical basis for the origin of the genetic code and the process of protein synthesis

NASA Technical Reports Server (NTRS)

1981-01-01

The principles upon which the process of protein synthesis and the genetic code were established are elucidated. Extensive work on nuclear magnetic resonance studies of both monomermonomer and monoamino acid polynucleotide interactions is included. A new method of general utility for studying any amino acid interacting with any polynucleotide was developed. This system involves the use of methyl esters of amino acids interacting with polynucleotides.

The genetic code as a periodic table: algebraic aspects.

PubMed

Bashford, J D; Jarvis, P D

2000-01-01

The systematics of indices of physico-chemical properties of codons and amino acids across the genetic code are examined. Using a simple numerical labelling scheme for nucleic acid bases, A=(-1,0), C=(0,-1), G=(0,1), U=(1,0), data can be fitted as low order polynomials of the six coordinates in the 64-dimensional codon weight space. The work confirms and extends the recent studies by Siemion et al. (1995. BioSystems 36, 231-238) of the conformational parameters. Fundamental patterns in the data such as codon periodicities, and related harmonics and reflection symmetries, are here associated with the structure of the set of basis monomials chosen for fitting. Results are plotted using the Siemion one-step mutation ring scheme, and variants thereof. The connections between the present work, and recent studies of the genetic code structure using dynamical symmetry algebras, are pointed out.

Emergence of Coding and its Specificity as a Physico-Informatic Problem

NASA Astrophysics Data System (ADS)

Wills, Peter R.; Nieselt, Kay; McCaskill, John S.

2015-06-01

We explore the origin-of-life consequences of the view that biological systems are demarcated from inanimate matter by their possession of referential information, which is processed computationally to control choices of specific physico-chemical events. Cells are cybernetic: they use genetic information in processes of communication and control, subjecting physical events to a system of integrated governance. The genetic code is the most obvious example of how cells use information computationally, but the historical origin of the usefulness of molecular information is not well understood. Genetic coding made information useful because it imposed a modular metric on the evolutionary search and thereby offered a general solution to the problem of finding catalysts of any specificity. We use the term "quasispecies symmetry breaking" to describe the iterated process of self-organisation whereby the alphabets of distinguishable codons and amino acids increased, step by step.

The Hypothesis that the Genetic Code Originated in Coupled Synthesis of Proteins and the Evolutionary Predecessors of Nucleic Acids in Primitive Cells

PubMed Central

Francis, Brian R.

2015-01-01

Although analysis of the genetic code has allowed explanations for its evolution to be proposed, little evidence exists in biochemistry and molecular biology to offer an explanation for the origin of the genetic code. In particular, two features of biology make the origin of the genetic code difficult to understand. First, nucleic acids are highly complicated polymers requiring numerous enzymes for biosynthesis. Secondly, proteins have a simple backbone with a set of 20 different amino acid side chains synthesized by a highly complicated ribosomal process in which mRNA sequences are read in triplets. Apparently, both nucleic acid and protein syntheses have extensive evolutionary histories. Supporting these processes is a complex metabolism and at the hub of metabolism are the carboxylic acid cycles. This paper advances the hypothesis that the earliest predecessor of the nucleic acids was a β-linked polyester made from malic acid, a highly conserved metabolite in the carboxylic acid cycles. In the β-linked polyester, the side chains are carboxylic acid groups capable of forming interstrand double hydrogen bonds. Evolution of the nucleic acids involved changes to the backbone and side chain of poly(β-d-malic acid). Conversion of the side chain carboxylic acid into a carboxamide or a longer side chain bearing a carboxamide group, allowed information polymers to form amide pairs between polyester chains. Aminoacylation of the hydroxyl groups of malic acid and its derivatives with simple amino acids such as glycine and alanine allowed coupling of polyester synthesis and protein synthesis. Use of polypeptides containing glycine and l-alanine for activation of two different monomers with either glycine or l-alanine allowed simple coded autocatalytic synthesis of polyesters and polypeptides and established the first genetic code. A primitive cell capable of supporting electron transport, thioester synthesis, reduction reactions, and synthesis of polyesters and polypeptides is proposed. The cell consists of an iron-sulfide particle enclosed by tholin, a heterogeneous organic material that is produced by Miller-Urey type experiments that simulate conditions on the early Earth. As the synthesis of nucleic acids evolved from β-linked polyesters, the singlet coding system for replication evolved into a four nucleotide/four amino acid process (AMP = aspartic acid, GMP = glycine, UMP = valine, CMP = alanine) and then into the triplet ribosomal process that permitted multiple copies of protein to be synthesized independent of replication. This hypothesis reconciles the “genetics first” and “metabolism first” approaches to the origin of life and explains why there are four bases in the genetic alphabet. PMID:25679748

EDGE 2017 R&D 100 Entry with Appendix

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

Chain, Patrick Sam Guy; Davenport, Karen Walston; Li, Po-E

Diabetes, infertility, cancer, and Alzheimer’s disease—the key to one day preventing or even curing such afflictions and diseases (both infectious and genetically driven) may be locked in our own genetic code and the code of microorganisms that inhabit our bodies. The study of this code, known as genomics, has recently become much more promising as a result of two things: (1) vast improvements in high-throughput, nextgeneration sequencing (NSG), and (2) an exponential decrease in the cost of such sequencing. For example, it originally cost approximately $3 billion to sequence the human genome; today, this genome could be resequenced for lessmore » than $1,000.« less

Genetic Code Expansion as a Tool to Study Regulatory Processes of Transcription

NASA Astrophysics Data System (ADS)

Schmidt, Moritz; Summerer, Daniel

2014-02-01

The expansion of the genetic code with noncanonical amino acids (ncAA) enables the chemical and biophysical properties of proteins to be tailored, inside cells, with a previously unattainable level of precision. A wide range of ncAA with functions not found in canonical amino acids have been genetically encoded in recent years and have delivered insights into biological processes that would be difficult to access with traditional approaches of molecular biology. A major field for the development and application of novel ncAA-functions has been transcription and its regulation. This is particularly attractive, since advanced DNA sequencing- and proteomics-techniques continue to deliver vast information on these processes on a global level, but complementing methodologies to study them on a detailed, molecular level and in living cells have been comparably scarce. In a growing number of studies, genetic code expansion has now been applied to precisely control the chemical properties of transcription factors, RNA polymerases and histones, and this has enabled new insights into their interactions, conformational changes, cellular localizations and the functional roles of posttranslational modifications.

Extraordinarily Adaptive Properties of the Genetically Encoded Amino Acids

PubMed Central

Ilardo, Melissa; Meringer, Markus; Freeland, Stephen; Rasulev, Bakhtiyor; Cleaves II, H. James

2015-01-01

Using novel advances in computational chemistry, we demonstrate that the set of 20 genetically encoded amino acids, used nearly universally to construct all coded terrestrial proteins, has been highly influenced by natural selection. We defined an adaptive set of amino acids as one whose members thoroughly cover relevant physico-chemical properties, or “chemistry space.” Using this metric, we compared the encoded amino acid alphabet to random sets of amino acids. These random sets were drawn from a computationally generated compound library containing 1913 alternative amino acids that lie within the molecular weight range of the encoded amino acids. Sets that cover chemistry space better than the genetically encoded alphabet are extremely rare and energetically costly. Further analysis of more adaptive sets reveals common features and anomalies, and we explore their implications for synthetic biology. We present these computations as evidence that the set of 20 amino acids found within the standard genetic code is the result of considerable natural selection. The amino acids used for constructing coded proteins may represent a largely global optimum, such that any aqueous biochemistry would use a very similar set. PMID:25802223

Program Instrumentation and Trace Analysis

NASA Technical Reports Server (NTRS)

Havelund, Klaus; Goldberg, Allen; Filman, Robert; Rosu, Grigore; Koga, Dennis (Technical Monitor)

2002-01-01

Several attempts have been made recently to apply techniques such as model checking and theorem proving to the analysis of programs. This shall be seen as a current trend to analyze real software systems instead of just their designs. This includes our own effort to develop a model checker for Java, the Java PathFinder 1, one of the very first of its kind in 1998. However, model checking cannot handle very large programs without some kind of abstraction of the program. This paper describes a complementary scalable technique to handle such large programs. Our interest is turned on the observation part of the equation: How much information can be extracted about a program from observing a single execution trace? It is our intention to develop a technology that can be applied automatically and to large full-size applications, with minimal modification to the code. We present a tool, Java PathExplorer (JPaX), for exploring execution traces of Java programs. The tool prioritizes scalability for completeness, and is directed towards detecting errors in programs, not to prove correctness. One core element in JPaX is an instrumentation package that allows to instrument Java byte code files to log various events when executed. The instrumentation is driven by a user provided script that specifies what information to log. Examples of instructions that such a script can contain are: 'report name and arguments of all called methods defined in class C, together with a timestamp'; 'report all updates to all variables'; and 'report all acquisitions and releases of locks'. In more complex instructions one can specify that certain expressions should be evaluated and even that certain code should be executed under various conditions. The instrumentation package can hence be seen as implementing Aspect Oriented Programming for Java in the sense that one can add functionality to a Java program without explicitly changing the code of the original program, but one rather writes an aspect and compiles it into the original program using the instrumentation. Another core element of JPaX is an observation package that supports the analysis of the generated event stream. Two kinds of analysis are currently supported. In temporal analysis the execution trace is evaluated against formulae written in temporal logic. We have implemented a temporal logic evaluator on finite traces using the Maude rewriting system from SRI International, USA. Temporal logic is defined in Maude by giving its syntax as a signature and its semantics as rewrite equations. The resulting semantics is extremely efficient and can handle event streams of hundreds of millions events in few minutes. Furthermore, the implementation is very succinct. The second form of even stream analysis supported is error pattern analysis where an execution trace is analyzed using various error detection algorithms that can identify error-prone programming practices that may potentially lead to errors in some different executions. Two such algorithms focusing on concurrency errors have been implemented in JPaX, one for deadlocks and the other for data races. It is important to note, that a deadlock or data race potential does not need to occur in order for its potential to be detected with these algorithms. This is what makes them very scalable in practice. The data race algorithm implemented is the Eraser algorithm from Compaq, however adopted to Java. The tool is currently being applied to a code base for controlling a spacecraft by the developers of that software in order to evaluate its applicability.

A Verification-Driven Approach to Traceability and Documentation for Auto-Generated Mathematical Software

NASA Technical Reports Server (NTRS)

Denney, Ewen W.; Fischer, Bernd

2009-01-01

Model-based development and automated code generation are increasingly used for production code in safety-critical applications, but since code generators are typically not qualified, the generated code must still be fully tested, reviewed, and certified. This is particularly arduous for mathematical and control engineering software which requires reviewers to trace subtle details of textbook formulas and algorithms to the code, and to match requirements (e.g., physical units or coordinate frames) not represented explicitly in models or code. Both tasks are complicated by the often opaque nature of auto-generated code. We address these problems by developing a verification-driven approach to traceability and documentation. We apply the AUTOCERT verification system to identify and then verify mathematical concepts in the code, based on a mathematical domain theory, and then use these verified traceability links between concepts, code, and verification conditions to construct a natural language report that provides a high-level structured argument explaining why and how the code uses the assumptions and complies with the requirements. We have applied our approach to generate review documents for several sub-systems of NASA s Project Constellation.

Force-Free Magnetic Fields Calculated from Automated Tracing of Coronal Loops with AIA/SDO

NASA Astrophysics Data System (ADS)

Aschwanden, M. J.

2013-12-01

One of the most realistic magnetic field models of the solar corona is a nonlinear force-free field (NLFFF) solution. There exist about a dozen numeric codes that compute NLFFF solutions based on extrapolations of photospheric vector magnetograph data. However, since the photosphere and lower chromosphere is not force-free, a suitable correction has to be applied to the lower boundary condition. Despite of such "pre-processing" corrections, the resulting theoretical magnetic field lines deviate substantially from observed coronal loop geometries. - Here we developed an alternative method that fits an analytical NLFFF approximation to the observed geometry of coronal loops. The 2D coordinates of the geometry of coronal loop structures observed with AIA/SDO are traced with the "Oriented Coronal CUrved Loop Tracing" (OCCULT-2) code, an automated pattern recognition algorithm that has demonstrated the fidelity in loop tracing matching visual perception. A potential magnetic field solution is then derived from a line-of-sight magnetogram observed with HMI/SDO, and an analytical NLFFF approximation is then forward-fitted to the twisted geometry of coronal loops. We demonstrate the performance of this magnetic field modeling method for a number of solar active regions, before and after major flares observed with SDO. The difference of the NLFFF and the potential field energies allows us then to compute the free magnetic energy, which is an upper limit of the energy that is released during a solar flare.

Predictions of Critical Heat Flux in Annular Pipes with TRACEv4.160 code

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

Jasiulevicius, Audrius; Macian-Juan, Rafael

2006-07-01

This paper presents the assessment of TRACE (version v4.160) against the Critical Heat Flux (CHF) experiments in annular tubes performed at the Royal Institute of Technology (KTH) in Stockholm, Sweden. The experimental database includes data for coolant mass fluxes between 250 and 2500 kg/m{sup 2}s and inlet subcooling of 10 and 40 K at a pressure of 70 bar. The work presented in this paper supplements the calculations of single round tube experiments carried out earlier and provides a broader scope of validated geometries. In addition to the Biasi and CISE-GE CHF correlations available in the code, a number ofmore » experimental points at low flow conditions are available for the annular geometry experiments, which also permitted the assessment of the Biasi/Zuber CHF correlation used in TRACE v4.160 for low flow conditions. Experiments with different axial power distribution were simulated and the effects of the axial power profile and the coolant inlet subcooling on the TRACE predictions were investigated. The results of this work show that the Biasi/Zuber correlation provides good estimation of the CHF at 70 bar, and, for the same conditions, the simulation of the annular experiments resulted in the calculation of lower CHF values compared to single-tube experiments. The analysis of the performance of the standard TRACE CHF correlations shows that the CISE-GE correlation yields critical qualities (quality at CHF) closer to the experimental values at 70 bar than the Biasi correlation for annular flow conditions. Regarding the power profile, the results of the TRACE calculations seem to be very sensitive to its shape, since, depending on the profile, different accuracies in the predictions were noted while other system conditions remained constant. The inlet coolant subcooling was also an important factor in the accuracy of TRACE CHF predictions. Thus, an increase in the inlet subcooling led to a clear improvement in the estimation of the critical quality with both Biasi and CISE-GE correlations. To complement the work, three additional CHF correlations were implemented in TRACE v4.160, namely the Bowring, Tong W-3 and Levitan-Lantsman CHF models, in order to assess the applicability of these correlations to simulate the CHF in annular tubes. The improvement of CHF predictions for low coolant mass flows (up to 1500 kg/m{sup 2}s) is noted when applying Bowring CHF correlation. However, the increase in the inlet subcooling increases the error in predicted critical quality with the Bowring correlation. The Levitan-Lantsman and Tong-W-3 correlations provide results similar to the Biasi model. Therefore, the most correct CHF predictions among the investigated correlations were obtained using CISE-GE model in the standard TRAC v4.160 code. (authors)« less

Assessing flow paths in a karst aquifer based on multiple dye tracing tests using stochastic simulation and the MODFLOW-CFP code

NASA Astrophysics Data System (ADS)

Assari, Amin; Mohammadi, Zargham

2017-09-01

Karst systems show high spatial variability of hydraulic parameters over small distances and this makes their modeling a difficult task with several uncertainties. Interconnections of fractures have a major role on the transport of groundwater, but many of the stochastic methods in use do not have the capability to reproduce these complex structures. A methodology is presented for the quantification of tortuosity using the single normal equation simulation (SNESIM) algorithm and a groundwater flow model. A training image was produced based on the statistical parameters of fractures and then used in the simulation process. The SNESIM algorithm was used to generate 75 realizations of the four classes of fractures in a karst aquifer in Iran. The results from six dye tracing tests were used to assign hydraulic conductivity values to each class of fractures. In the next step, the MODFLOW-CFP and MODPATH codes were consecutively implemented to compute the groundwater flow paths. The 9,000 flow paths obtained from the MODPATH code were further analyzed to calculate the tortuosity factor. Finally, the hydraulic conductivity values calculated from the dye tracing experiments were refined using the actual flow paths of groundwater. The key outcomes of this research are: (1) a methodology for the quantification of tortuosity; (2) hydraulic conductivities, that are incorrectly estimated (biased low) with empirical equations that assume Darcian (laminar) flow with parallel rather than tortuous streamlines; and (3) an understanding of the scale-dependence and non-normal distributions of tortuosity.

Epigenetics: a new frontier in dentistry.

PubMed

Williams, S D; Hughes, T E; Adler, C J; Brook, A H; Townsend, G C

2014-06-01

In 2007, only four years after the completion of the Human Genome Project, the journal Science announced that epigenetics was the 'breakthrough of the year'. Time magazine placed it second in the top 10 discoveries of 2009. While our genetic code (i.e. our DNA) contains all of the information to produce the elements we require to function, our epigenetic code determines when and where genes in the genetic code are expressed. Without the epigenetic code, the genetic code is like an orchestra without a conductor. Although there is now a substantial amount of published research on epigenetics in medicine and biology, epigenetics in dental research is in its infancy. However, epigenetics promises to become increasingly relevant to dentistry because of the role it plays in gene expression during development and subsequently potentially influencing oral disease susceptibility. This paper provides a review of the field of epigenetics aimed specifically at oral health professionals. It defines epigenetics, addresses the underlying concepts and provides details about specific epigenetic molecular mechanisms. Further, we discuss some of the key areas where epigenetics is implicated, and review the literature on epigenetics research in dentistry, including its relevance to clinical disciplines. This review considers some implications of epigenetics for the future of dental practice, including a 'personalized medicine' approach to the management of common oral diseases. © 2014 Australian Dental Association.

A novel reverse genetics system for production of infectious West Nile virus using homologous recombination in mammalian cells.

PubMed

Kobayashi, Shintaro; Yoshii, Kentaro; Hirano, Minato; Muto, Memi; Kariwa, Hiroaki

2017-02-01

Reverse genetics systems facilitate investigation of many aspects of the life cycle and pathogenesis of viruses. However, genetic instability in Escherichia coli has hampered development of a reverse genetics system for West Nile virus (WNV). In this study, we developed a novel reverse genetics system for WNV based on homologous recombination in mammalian cells. Introduction of the DNA fragment coding for the WNV structural protein together with a DNA-based replicon resulted in the release of infectious WNV. The growth rate and plaque size of the recombinant virus were almost identical to those of the parent WNV. Furthermore, chimeric WNV was produced by introducing the DNA fragment coding for the structural protein and replicon plasmid derived from various strains. Here, we report development of a novel system that will facilitate research into WNV infection. Copyright © 2016 Elsevier B.V. All rights reserved.

Contamination Analysis Tools

NASA Technical Reports Server (NTRS)

Brieda, Lubos

2015-01-01

This talk presents 3 different tools developed recently for contamination analysis:HTML QCM analyzer: runs in a web browser, and allows for data analysis of QCM log filesJava RGA extractor: can load in multiple SRS.ana files and extract pressure vs. time dataC++ Contamination Simulation code: 3D particle tracing code for modeling transport of dust particulates and molecules. Uses residence time to determine if molecules stick. Particulates can be sampled from IEST-STD-1246 and be accelerated by aerodynamic forces.

The Human Proteome Project: Unlocking the Mysteries of Human Life and Unleashing Its Potential

DTIC Science & Technology

2011-02-16

Australasian Genetics Resource Book. June 2007. Accessed September 27, 2010. www.genetics.com.au/pdf/factsheets/fs24.pdf. 2 White House, Office of...Project and Beyond." The Australasian Genetics Resource Book. June 2007. Accessed September 27, 2010. www.genetics.com.au/pdf/factsheets/fs24.pdf...9 Centre for Genetics Education. "The Human Genetic Code – The Human Genome Project and Beyond." The Australasian Genetics Resource Book. June

An experimental investigation of multi-element airfoil ice accretion and resulting performance degradation

NASA Technical Reports Server (NTRS)

Potapczuk, Mark G.; Berkowitz, Brian M.

1989-01-01

An investigation of the ice accretion pattern and performance characteristics of a multi-element airfoil was undertaken in the NASA Lewis 6- by 9-Foot Icing Research Tunnel. Several configurations of main airfoil, slat, and flaps were employed to examine the effects of ice accretion and provide further experimental information for code validation purposes. The text matrix consisted of glaze, rime, and mixed icing conditions. Airflow and icing cloud conditions were set to correspond to those typical of the operating environment anticipated tor a commercial transport vehicle. Results obtained included ice profile tracings, photographs of the ice accretions, and force balance measurements obtained both during the accretion process and in a post-accretion evaluation over a range of angles of attack. The tracings and photographs indicated significant accretions on the slat leading edge, in gaps between slat or flaps and the main wing, on the flap leading-edge surfaces, and on flap lower surfaces. Force measurments indicate the possibility of severe performance degradation, especially near C sub Lmax, for both light and heavy ice accretion and performance analysis codes presently in use. The LEWICE code was used to evaluate the ice accretion shape developed during one of the rime ice tests. The actual ice shape was then evaluated, using a Navier-Strokes code, for changes in performance characteristics. These predicted results were compared to the measured results and indicate very good agreement.

Application of a GPU-Assisted Maxwell Code to Electromagnetic Wave Propagation in ITER

NASA Astrophysics Data System (ADS)

Kubota, S.; Peebles, W. A.; Woodbury, D.; Johnson, I.; Zolfaghari, A.

2014-10-01

The Low Field Side Reflectometer (LSFR) on ITER is envisioned to provide capabilities for electron density profile and fluctuations measurements in both the plasma core and edge. The current design for the Equatorial Port Plug 11 (EPP11) employs seven monostatic antennas for use with both fixed-frequency and swept-frequency systems. The present work examines the characteristics of this layout using the 3-D version of the GPU-Assisted Maxwell Code (GAMC-3D). Previous studies in this area were performed with either 2-D full wave codes or 3-D ray- and beam-tracing. GAMC-3D is based on the FDTD method and can be run with either a fixed-frequency or modulated (e.g. FMCW) source, and with either a stationary or moving target (e.g. Doppler backscattering). The code is designed to run on a single NVIDIA Tesla GPU accelerator, and utilizes a technique based on the moving window method to overcome the size limitation of the onboard memory. Effects such as beam drift, linear mode conversion, and diffraction/scattering will be examined. Comparisons will be made with beam-tracing calculations using the complex eikonal method. Supported by U.S. DoE Grants DE-FG02-99ER54527 and DE-AC02-09CH11466, and the DoE SULI Program at PPPL.

A novel nuclear genetic code alteration in yeasts and the evolution of codon reassignment in eukaryotes.

PubMed

Mühlhausen, Stefanie; Findeisen, Peggy; Plessmann, Uwe; Urlaub, Henning; Kollmar, Martin

2016-07-01

The genetic code is the cellular translation table for the conversion of nucleotide sequences into amino acid sequences. Changes to the meaning of sense codons would introduce errors into almost every translated message and are expected to be highly detrimental. However, reassignment of single or multiple codons in mitochondria and nuclear genomes, although extremely rare, demonstrates that the code can evolve. Several models for the mechanism of alteration of nuclear genetic codes have been proposed (including "codon capture," "genome streamlining," and "ambiguous intermediate" theories), but with little resolution. Here, we report a novel sense codon reassignment in Pachysolen tannophilus, a yeast related to the Pichiaceae. By generating proteomics data and using tRNA sequence comparisons, we show that Pachysolen translates CUG codons as alanine and not as the more usual leucine. The Pachysolen tRNACAG is an anticodon-mutated tRNA(Ala) containing all major alanine tRNA recognition sites. The polyphyly of the CUG-decoding tRNAs in yeasts is best explained by a tRNA loss driven codon reassignment mechanism. Loss of the CUG-tRNA in the ancient yeast is followed by gradual decrease of respective codons and subsequent codon capture by tRNAs whose anticodon is not part of the aminoacyl-tRNA synthetase recognition region. Our hypothesis applies to all nuclear genetic code alterations and provides several testable predictions. We anticipate more codon reassignments to be uncovered in existing and upcoming genome projects. © 2016 Mühlhausen et al.; Published by Cold Spring Harbor Laboratory Press.

Does the Genetic Code Have A Eukaryotic Origin?

PubMed Central

Zhang, Zhang; Yu, Jun

2013-01-01

In the RNA world, RNA is assumed to be the dominant macromolecule performing most, if not all, core “house-keeping” functions. The ribo-cell hypothesis suggests that the genetic code and the translation machinery may both be born of the RNA world, and the introduction of DNA to ribo-cells may take over the informational role of RNA gradually, such as a mature set of genetic code and mechanism enabling stable inheritance of sequence and its variation. In this context, we modeled the genetic code in two content variables—GC and purine contents—of protein-coding sequences and measured the purine content sensitivities for each codon when the sensitivity (% usage) is plotted as a function of GC content variation. The analysis leads to a new pattern—the symmetric pattern—where the sensitivity of purine content variation shows diagonally symmetry in the codon table more significantly in the two GC content invariable quarters in addition to the two existing patterns where the table is divided into either four GC content sensitivity quarters or two amino acid diversity halves. The most insensitive codon sets are GUN (valine) and CAN (CAR for asparagine and CAY for aspartic acid) and the most biased amino acid is valine (always over-estimated) followed by alanine (always under-estimated). The unique position of valine and its codons suggests its key roles in the final recruitment of the complete codon set of the canonical table. The distinct choice may only be attributable to sequence signatures or signals of splice sites for spliceosomal introns shared by all extant eukaryotes. PMID:23402863

Xenobiology: State-of-the-Art, Ethics, and Philosophy of New-to-Nature Organisms.

PubMed

Schmidt, Markus; Pei, Lei; Budisa, Nediljko

The basic chemical constitution of all living organisms in the context of carbon-based chemistry consists of a limited number of small molecules and polymers. Until the twenty-first century, biology was mainly an analytical science and has now reached a point where it merges with engineering science, paving the way for synthetic biology. One of the objectives of synthetic biology is to try to change the chemical compositions of living cells, that is, to create an artificial biological diversity, which in turn fosters a new sub-field of synthetic biology, xenobiology. In particular, the genetic code in living systems is based on highly standardized chemistry composed of the same "letters" or nucleotides as informational polymers (DNA, RNA) and the 20 amino acids which serve as basic building blocks for proteins. The universality of the genetic code enables not only vertical gene transfer within the same species but also horizontal gene transfer across biological taxa, which require a high degree of standardization and interconnectivity. Although some minor alterations of the standard genetic code are found in nature (e.g., proteins containing non-conical amino acids exist in nature, and some organisms use alternated coding systems), all structurally deep chemistry changes within living systems are generally lethal, making the creation of artificial biological system an extremely difficult challenge.In this context, one of the great challenges for bioscience is the development of a strategy for expanding the standard basic chemical repertoire of living cells. Attempts to alter the meaning of the genetic information stored in DNA as an informational polymer by changing the chemistry of the polymer (i.e., xeno-nucleic acids) or by changes in the genetic code have already yielded successful results. In the future this should enable the partial or full redirection of the biological information flow to generate "new" version(s) of the genetic code derived from the "old" biological world.In addition to the scientific challenges, the attempt to increase biochemical diversity also raises important ethical and philosophical issues. Although promotors of this branch of synthetic biology highlight the many potential applications to come (e.g., novel tools for diagnostics and fighting infection diseases), such developments could also bring risks affecting social, political, and other structures of nearly all societies.

SPOT satellite mapping of Ice Stream B

NASA Technical Reports Server (NTRS)

Merry, Carolyn J.

1993-01-01

Numerous features of glaciological significance appear on two adjoining SPOT High Resolution Visible (HRV) images that cover the onset region of ice stream B. Many small-scale features, such as crevasses and drift plumes, have been previously observed in aerial photography. Subtle features, such as long flow traces that have not been mapped previously, are also clear in the satellite imagery. Newly discovered features include ladder-like runners and rungs within certain shear margins, flow traces that are parallel to ice flow, unusual crevasse patterns, and flow traces originating within shear margins. An objective of our work is to contribute to an understanding of the genesis of the features observed in satellite imagery. The genetic possibilities for flow traces, other lineations, bands of transverse crevasses, shear margins, mottles, and lumps and warps are described.

Active Inference and Learning in the Cerebellum.

PubMed

Friston, Karl; Herreros, Ivan

2016-09-01

This letter offers a computational account of Pavlovian conditioning in the cerebellum based on active inference and predictive coding. Using eyeblink conditioning as a canonical paradigm, we formulate a minimal generative model that can account for spontaneous blinking, startle responses, and (delay or trace) conditioning. We then establish the face validity of the model using simulated responses to unconditioned and conditioned stimuli to reproduce the sorts of behavior that are observed empirically. The scheme's anatomical validity is then addressed by associating variables in the predictive coding scheme with nuclei and neuronal populations to match the (extrinsic and intrinsic) connectivity of the cerebellar (eyeblink conditioning) system. Finally, we try to establish predictive validity by reproducing selective failures of delay conditioning, trace conditioning, and extinction using (simulated and reversible) focal lesions. Although rather metaphorical, the ensuing scheme can account for a remarkable range of anatomical and neurophysiological aspects of cerebellar circuitry-and the specificity of lesion-deficit mappings that have been established experimentally. From a computational perspective, this work shows how conditioning or learning can be formulated in terms of minimizing variational free energy (or maximizing Bayesian model evidence) using exactly the same principles that underlie predictive coding in perception.

[Genetic diversity of modern Russian durum wheat cultivars at the gliadin-coding loci].

PubMed

Kudriavtsev, A M; Dedova, L V; Mel'nik, V A; Shishkina, A A; Upelniek, V P; Novosel'skaia-Dragovich, A Iu

2014-05-01

The allelic diversity at four gliadin-coding loci was examined in modern cultivars of the spring and winter durum wheat Triticum durum Desf. Comparative analysis of the allelic diversity showed that the gene pools of these two types of durum wheat, having different life styles, were considerably different. For the modern spring durum wheat cultivars, a certain reduction of the genetic diversity was observed compared to the cultivars bred in the 20th century.

New insights into mitogenomic phylogeny and copy number in eight indigenous sheep populations based on the ATP synthase and cytochrome c oxidase genes.

PubMed

Xiao, P; Niu, L L; Zhao, Q J; Chen, X Y; Wang, L J; Li, L; Zhang, H P; Guo, J Z; Xu, H Y; Zhong, T

2017-11-16

The origins and phylogeny of different sheep breeds has been widely studied using polymorphisms within the mitochondrial hypervariable region. However, little is known about the mitochondrial DNA (mtDNA) content and phylogeny based on mtDNA protein-coding genes. In this study, we assessed the phylogeny and copy number of the mtDNA in eight indigenous (population size, n=184) and three introduced (n=66) sheep breeds in China based on five mitochondrial coding genes (COX1, COX2, ATP8, ATP6 and COX3). The mean haplotype and nucleotide diversities were 0.944 and 0.00322, respectively. We identified a correlation between the lineages distribution and the genetic distance, whereby Valley-type Tibetan sheep had a closer genetic relationship with introduced breeds (Dorper, Poll Dorset and Suffolk) than with other indigenous breeds. Similarly, the Median-joining profile of haplotypes revealed the distribution of clusters according to genetic differences. Moreover, copy number analysis based on the five mitochondrial coding genes was affected by the genetic distance combining with genetic phylogeny; we also identified obvious non-synonymous mutations in ATP6 between the different levels of copy number expressions. These results imply that differences in mitogenomic compositions resulting from geographical separation lead to differences in mitochondrial function.

An investigation of messy genetic algorithms

NASA Technical Reports Server (NTRS)

Goldberg, David E.; Deb, Kalyanmoy; Korb, Bradley

1990-01-01

Genetic algorithms (GAs) are search procedures based on the mechanics of natural selection and natural genetics. They combine the use of string codings or artificial chromosomes and populations with the selective and juxtapositional power of reproduction and recombination to motivate a surprisingly powerful search heuristic in many problems. Despite their empirical success, there has been a long standing objection to the use of GAs in arbitrarily difficult problems. A new approach was launched. Results to a 30-bit, order-three-deception problem were obtained using a new type of genetic algorithm called a messy genetic algorithm (mGAs). Messy genetic algorithms combine the use of variable-length strings, a two-phase selection scheme, and messy genetic operators to effect a solution to the fixed-coding problem of standard simple GAs. The results of the study of mGAs in problems with nonuniform subfunction scale and size are presented. The mGA approach is summarized, both its operation and the theory of its use. Experiments on problems of varying scale, varying building-block size, and combined varying scale and size are presented.

Intact coding region of the serotonin transporter gene in obsessive-compulsive disorder

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

Altemus, M.; Murphy, D.L.; Greenberg, B.

1996-07-26

Epidemiologic studies indicate that obsessive-compulsive disorder is genetically transmitted in some families, although no genetic abnormalities have been identified in individuals with this disorder. The selective response of obsessive-compulsive disorder to treatment with agents which block serotonin reuptake suggests the gene coding for the serotonin transporter as a candidate gene. The primary structure of the serotonin-transporter coding region was sequenced in 22 patients with obsessive-compulsive disorder, using direct PCR sequencing of cDNA synthesized from platelet serotonin-transporter mRNA. No variations in amino acid sequence were found among the obsessive-compulsive disorder patients or healthy controls. These results do not support a rolemore » for alteration in the primary structure of the coding region of the serotonin-transporter gene in the pathogenesis of obsessive-compulsive disorder. 27 refs.« less

Coding, Constant Comparisons, and Core Categories: A Worked Example for Novice Constructivist Grounded Theorists.

PubMed

Giles, Tracey M; de Lacey, Sheryl; Muir-Cochrane, Eimear

2016-01-01

Grounded theory method has been described extensively in the literature. Yet, the varying processes portrayed can be confusing for novice grounded theorists. This article provides a worked example of the data analysis phase of a constructivist grounded theory study that examined family presence during resuscitation in acute health care settings. Core grounded theory methods are exemplified, including initial and focused coding, constant comparative analysis, memo writing, theoretical sampling, and theoretical saturation. The article traces the construction of the core category "Conditional Permission" from initial and focused codes, subcategories, and properties, through to its position in the final substantive grounded theory.

Trace conditioning in insects—keep the trace!

PubMed Central

Dylla, Kristina V.; Galili, Dana S.; Szyszka, Paul; Lüdke, Alja

2013-01-01

Trace conditioning is a form of associative learning that can be induced by presenting a conditioned stimulus (CS) and an unconditioned stimulus (US) following each other, but separated by a temporal gap. This gap distinguishes trace conditioning from classical delay conditioning, where the CS and US overlap. To bridge the temporal gap between both stimuli and to form an association between CS and US in trace conditioning, the brain must keep a neural representation of the CS after its termination—a stimulus trace. Behavioral and physiological studies on trace and delay conditioning revealed similarities between the two forms of learning, like similar memory decay and similar odor identity perception in invertebrates. On the other hand differences were reported also, like the requirement of distinct brain structures in vertebrates or disparities in molecular mechanisms in both vertebrates and invertebrates. For example, in commonly used vertebrate conditioning paradigms the hippocampus is necessary for trace but not for delay conditioning, and Drosophila delay conditioning requires the Rutabaga adenylyl cyclase (Rut-AC), which is dispensable in trace conditioning. It is still unknown how the brain encodes CS traces and how they are associated with a US in trace conditioning. Insects serve as powerful models to address the mechanisms underlying trace conditioning, due to their simple brain anatomy, behavioral accessibility and established methods of genetic interference. In this review we summarize the recent progress in insect trace conditioning on the behavioral and physiological level and emphasize similarities and differences compared to delay conditioning. Moreover, we examine proposed molecular and computational models and reassess different experimental approaches used for trace conditioning. PMID:23986710

Performance Analysis of Multilevel Parallel Applications on Shared Memory Architectures

NASA Technical Reports Server (NTRS)

Jost, Gabriele; Jin, Haoqiang; Labarta, Jesus; Gimenez, Judit; Caubet, Jordi; Biegel, Bryan A. (Technical Monitor)

2002-01-01

In this paper we describe how to apply powerful performance analysis techniques to understand the behavior of multilevel parallel applications. We use the Paraver/OMPItrace performance analysis system for our study. This system consists of two major components: The OMPItrace dynamic instrumentation mechanism, which allows the tracing of processes and threads and the Paraver graphical user interface for inspection and analyses of the generated traces. We describe how to use the system to conduct a detailed comparative study of a benchmark code implemented in five different programming paradigms applicable for shared memory

On Francis Crick, the genetic code, and a clever kid.

PubMed

Goldstein, Bob

2018-04-02

A few years ago, Francis Crick's son told me a story that I can't get out of my mind. I had contacted Michael Crick by email while digging through the background of the researchers who had cracked the genetic code in the 1960s. Francis had died in 2004, and I was contacting some of the people who knew him when he was struggling to decipher the code. Francis didn't appear to struggle often - he is known mostly for his successes - and, as it turns out, this one well-known struggle may have had a clue sitting just barely out of sight. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Mind at Every Stage Has Its Own Logic: John Dewey as Genetic Psychologist

ERIC Educational Resources Information Center

Fallace, Thomas Daniel

2010-01-01

In this essay Thomas Fallace argues that John Dewey can best be described as a pragmatic historicist and a genetic psychologist. This means that Dewey believed that the best way to understand any idea, phenomenon, or entity is to trace its history, that the history of the individual and race pass through distinct stages of development, and that…

Identification of common, unique and polymorphic microsatellites among 73 cyanobacterial genomes.

PubMed

Kabra, Ritika; Kapil, Aditi; Attarwala, Kherunnisa; Rai, Piyush Kant; Shanker, Asheesh

2016-04-01

Microsatellites also known as Simple Sequence Repeats are short tandem repeats of 1-6 nucleotides. These repeats are found in coding as well as non-coding regions of both prokaryotic and eukaryotic genomes and play a significant role in the study of gene regulation, genetic mapping, DNA fingerprinting and evolutionary studies. The availability of 73 complete genome sequences of cyanobacteria enabled us to mine and statistically analyze microsatellites in these genomes. The cyanobacterial microsatellites identified through bioinformatics analysis were stored in a user-friendly database named CyanoSat, which is an efficient data representation and query system designed using ASP.net. The information in CyanoSat comprises of perfect, imperfect and compound microsatellites found in coding, non-coding and coding-non-coding regions. Moreover, it contains PCR primers with 200 nucleotides long flanking region. The mined cyanobacterial microsatellites can be freely accessed at www.compubio.in/CyanoSat/home.aspx. In addition to this 82 polymorphic, 13,866 unique and 2390 common microsatellites were also detected. These microsatellites will be useful in strain identification and genetic diversity studies of cyanobacteria.

Review: Authentication and traceability of foods from animal origin by polymerase chain reaction-based capillary electrophoresis.

PubMed

Rodríguez-Ramírez, Roberto; González-Córdova, Aarón F; Vallejo-Cordoba, Belinda

2011-01-31

This work presents an overview of the applicability of PCR-based capillary electrophoresis (CE) in food authentication and traceability of foods from animal origin. Analytical approaches for authenticating and tracing meat and meat products and fish and seafood products are discussed. Particular emphasis will be given to the usefulness of genotyping in food tracing by using CE-based genetic analyzers. Copyright © 2010 Elsevier B.V. All rights reserved.

Assessing the readiness of precision medicine interoperabilty: An exploratory study of the National Institutes of Health genetic testing registry.

PubMed

Ronquillo, Jay G; Weng, Chunhua; Lester, William T

2017-11-17

  Precision medicine involves three major innovations currently taking place in healthcare:  electronic health records, genomics, and big data.  A major challenge for healthcare providers, however, is understanding the readiness for practical application of initiatives like precision medicine.   To better understand the current state and challenges of precision medicine interoperability using a national genetic testing registry as a starting point, placed in the context of established interoperability formats.   We performed an exploratory analysis of the National Institutes of Health Genetic Testing Registry.  Relevant standards included Health Level Seven International Version 3 Implementation Guide for Family History, the Human Genome Organization Gene Nomenclature Committee (HGNC) database, and Systematized Nomenclature of Medicine - Clinical Terms (SNOMED CT).  We analyzed the distribution of genetic testing laboratories, genetic test characteristics, and standardized genome/clinical code mappings, stratified by laboratory setting. There were a total of 25472 genetic tests from 240 laboratories testing for approximately 3632 distinct genes.  Most tests focused on diagnosis, mutation confirmation, and/or risk assessment of germline mutations that could be passed to offspring.  Genes were successfully mapped to all HGNC identifiers, but less than half of tests mapped to SNOMED CT codes, highlighting significant gaps when linking genetic tests to standardized clinical codes that explain the medical motivations behind test ordering.  Conclusion:  While precision medicine could potentially transform healthcare, successful practical and clinical application will first require the comprehensive and responsible adoption of interoperable standards, terminologies, and formats across all aspects of the precision medicine pipeline.

Certifying Auto-Generated Flight Code

NASA Technical Reports Server (NTRS)

Denney, Ewen

2008-01-01

Model-based design and automated code generation are being used increasingly at NASA. Many NASA projects now use MathWorks Simulink and Real-Time Workshop for at least some of their modeling and code development. However, there are substantial obstacles to more widespread adoption of code generators in safety-critical domains. Since code generators are typically not qualified, there is no guarantee that their output is correct, and consequently the generated code still needs to be fully tested and certified. Moreover, the regeneration of code can require complete recertification, which offsets many of the advantages of using a generator. Indeed, manual review of autocode can be more challenging than for hand-written code. Since the direct V&V of code generators is too laborious and complicated due to their complex (and often proprietary) nature, we have developed a generator plug-in to support the certification of the auto-generated code. Specifically, the AutoCert tool supports certification by formally verifying that the generated code is free of different safety violations, by constructing an independently verifiable certificate, and by explaining its analysis in a textual form suitable for code reviews. The generated documentation also contains substantial tracing information, allowing users to trace between model, code, documentation, and V&V artifacts. This enables missions to obtain assurance about the safety and reliability of the code without excessive manual V&V effort and, as a consequence, eases the acceptance of code generators in safety-critical contexts. The generation of explicit certificates and textual reports is particularly well-suited to supporting independent V&V. The primary contribution of this approach is the combination of human-friendly documentation with formal analysis. The key technical idea is to exploit the idiomatic nature of auto-generated code in order to automatically infer logical annotations. The annotation inference algorithm itself is generic, and parametrized with respect to a library of coding patterns that depend on the safety policies and the code generator. The patterns characterize the notions of definitions and uses that are specific to the given safety property. For example, for initialization safety, definitions correspond to variable initializations while uses are statements which read a variable, whereas for array bounds safety, definitions are the array declarations, while uses are statements which access an array variable. The inferred annotations are thus highly dependent on the actual program and the properties being proven. The annotations, themselves, need not be trusted, but are crucial to obtain the automatic formal verification of the safety properties without requiring access to the internals of the code generator. The approach has been applied to both in-house and commercial code generators, but is independent of the particular generator used. It is currently being adapted to flight code generated using MathWorks Real-Time Workshop, an automatic code generator that translates from Simulink/Stateflow models into embedded C code.

Worthwhile optical method for free-form mirrors qualification

NASA Astrophysics Data System (ADS)

Sironi, G.; Canestrari, R.; Toso, G.; Pareschi, G.

2013-09-01

We present an optical method for free-form mirrors qualification developed by the Italian National Institute for Astrophysics (INAF) in the context of the ASTRI (Astrofisica con Specchi a Tecnologia Replicante Italiana) Project which includes, among its items, the design, development and installation of a dual-mirror telescope prototype for the Cherenkov Telescope Array (CTA) observatory. The primary mirror panels of the telescope prototype are free-form concave mirrors with few microns accuracy required on the shape error. The developed technique is based on the synergy between a Ronchi-like optical test performed on the reflecting surface and the image, obtained by means of the TraceIT ray-tracing proprietary code, a perfect optics should generate in the same configuration. This deflectometry test allows the reconstruction of the slope error map that the TraceIT code can process to evaluate the measured mirror optical performance at the telescope focus. The advantages of the proposed method is that it substitutes the use of 3D coordinates measuring machine reducing production time and costs and offering the possibility to evaluate on-site the mirror image quality at the focus. In this paper we report the measuring concept and compare the obtained results to the similar ones obtained processing the shape error acquired by means of a 3D coordinates measuring machine.

Ray tracing method for the evaluation of grazing incidence x-ray telescopes described by spatially sampled surfaces.

PubMed

Yu, Jun; Shen, Zhengxiang; Sheng, Pengfeng; Wang, Xiaoqiang; Hailey, Charles J; Wang, Zhanshan

2018-03-01

The nested grazing incidence telescope can achieve a large collecting area in x-ray astronomy, with a large number of closely packed, thin conical mirrors. Exploiting the surface metrological data, the ray tracing method used to reconstruct the shell surface topography and evaluate the imaging performance is a powerful tool to assist iterative improvement in the fabrication process. However, current two-dimensional (2D) ray tracing codes, especially when utilized with densely sampled surface shape data, may not provide sufficient accuracy of reconstruction and are computationally cumbersome. In particular, 2D ray tracing currently employed considers coplanar rays and thus simulates only these rays along the meridional plane. This captures axial figure errors but leaves other important errors, such as roundness errors, unaccounted for. We introduce a semianalytic, three-dimensional (3D) ray tracing approach for x-ray optics that overcomes these shortcomings. And the present method is both computationally fast and accurate. We first introduce the principles and the computational details of this 3D ray tracing method. Then the computer simulations of this approach compared to 2D ray tracing are demonstrated, using an ideal conic Wolter-I telescope for benchmarking. Finally, the present 3D ray tracing is used to evaluate the performance of a prototype x-ray telescope fabricated for the enhanced x-ray timing and polarization mission.

Propagation Effects of Wind and Temperature on Acoustic Ground Contour Levels

NASA Technical Reports Server (NTRS)

Heath, Stephanie L.; McAninch, Gerry L.

2006-01-01

Propagation characteristics for varying wind and temperature atmospheric conditions are identified using physically-limiting propagation angles to define shadow boundary regions. These angles are graphically illustrated for various wind and temperature cases using a newly developed ray-tracing propagation code.

Systematic screening for mutations in the promoter and the coding region of the 5-HT{sub 1A} gene

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

Erdmann, J.; Shimron-Abarbanell, D.; Cichon, S.

1995-10-09

In the present study we sought to identify genetic variation in the 5-HT{sub 1A} receptor gene which through alteration of protein function or level of expression might contribute to the genetic predisposition to neuropsychiatric diseases. Genomic DNA samples from 159 unrelated subjects (including 45 schizophrenic, 46 bipolar affective, and 43 patients with Tourette`s syndrome, as well as 25 healthy controls) were investigated by single-strand conformation analysis. Overlapping PCR (polymerase chain reaction) fragments covered the whole coding sequence as well as the 5{prime} untranslated region of the 5-HT{sub 1A} gene. The region upstream to the coding sequence we investigated contains amore » functional promoter. We found two rare nucleotide sequence variants. Both mutations are located in the coding region of the gene: a coding mutation (A{yields}G) in nucleotide position 82 which leads to an amino acid exchange (Ile{yields}Val) in position 28 of the receptor protein and a silent mutation (C{yields}T) in nucleotide position 549. The occurrence of the Ile-28-Val substitution was studied in an extended sample of patients (n = 352) and controls (n = 210) but was found in similar frequencies in all groups. Thus, this mutation is unlikely to play a significant role in the genetic predisposition to the diseases investigated. In conclusion, our study does not provide evidence that the 5-HT{sub 1A} gene plays either a major or a minor role in the genetic predisposition to schizophrenia, bipolar affective disorder, or Tourette`s syndrome. 29 refs., 4 figs., 1 tab.« less

Biosamples, genomics, and human rights: context and content of Iceland's Biobanks Act.

PubMed

Winickoff, D E

2001-01-01

In recent years, human DNA sampling and collection has accelerated without the development of enforceable rules protecting the human rights of donors. The need for regulation of biobanking is especially acute in Iceland, whose parliament has granted a for-profit corporation, deCODE Genetics, an exclusive license to create a centralized database of health records for studies on human genetic variation. Until recently, how deCODE Genetics would get genetic material for its genotypic-phenotypic database remained unclear. However, in May 2000, the Icelandic Parliament passed the Icelandic Biobanks Act, the world's earliest attempt to construct binding rules for the use of biobanks in scientific research. Unfortunately, Iceland has lost an opportunity for bringing clear and ethically sound standards to the use of human biological samples in deCODE's database and in other projects: the Biobanks Act has extended a notion of "presumed consent" from the use of medical records to the use of patients' biological samples; worse, the act has made it possible--perhaps likely--that a donor's wish to withdraw his/her sample will be ignored. Inadequacies in the Act's legislative process help account for these deficiencies in the protection of donor autonomy.

Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment.

PubMed

Villanueva, Pía; Nudel, Ron; Hoischen, Alexander; Fernández, María Angélica; Simpson, Nuala H; Gilissen, Christian; Reader, Rose H; Jara, Lillian; Echeverry, María Magdalena; Echeverry, Maria Magdalena; Francks, Clyde; Baird, Gillian; Conti-Ramsden, Gina; O'Hare, Anne; Bolton, Patrick F; Hennessy, Elizabeth R; Palomino, Hernán; Carvajal-Carmona, Luis; Veltman, Joris A; Cazier, Jean-Baptiste; De Barbieri, Zulema; Fisher, Simon E; Newbury, Dianne F

2015-03-01

Children affected by Specific Language Impairment (SLI) fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techniques to investigate an admixed isolated founder population from the Robinson Crusoe Island (Chile), who are affected by a high incidence of SLI, increasing the power to discover contributory genetic factors. We utilize exome sequencing in selected individuals from this population to identify eight coding variants that are of putative significance. We then apply association analyses across the wider population to highlight a single rare coding variant (rs144169475, Minor Allele Frequency of 4.1% in admixed South American populations) in the NFXL1 gene that confers a nonsynonymous change (N150K) and is significantly associated with language impairment in the Robinson Crusoe population (p = 2.04 × 10-4, 8 variants tested). Subsequent sequencing of NFXL1 in 117 UK SLI cases identified four individuals with heterozygous variants predicted to be of functional consequence. We conclude that coding variants within NFXL1 confer an increased risk of SLI within a complex genetic model.

Analysis of protein-coding genetic variation in 60,706 humans.

PubMed

Lek, Monkol; Karczewski, Konrad J; Minikel, Eric V; Samocha, Kaitlin E; Banks, Eric; Fennell, Timothy; O'Donnell-Luria, Anne H; Ware, James S; Hill, Andrew J; Cummings, Beryl B; Tukiainen, Taru; Birnbaum, Daniel P; Kosmicki, Jack A; Duncan, Laramie E; Estrada, Karol; Zhao, Fengmei; Zou, James; Pierce-Hoffman, Emma; Berghout, Joanne; Cooper, David N; Deflaux, Nicole; DePristo, Mark; Do, Ron; Flannick, Jason; Fromer, Menachem; Gauthier, Laura; Goldstein, Jackie; Gupta, Namrata; Howrigan, Daniel; Kiezun, Adam; Kurki, Mitja I; Moonshine, Ami Levy; Natarajan, Pradeep; Orozco, Lorena; Peloso, Gina M; Poplin, Ryan; Rivas, Manuel A; Ruano-Rubio, Valentin; Rose, Samuel A; Ruderfer, Douglas M; Shakir, Khalid; Stenson, Peter D; Stevens, Christine; Thomas, Brett P; Tiao, Grace; Tusie-Luna, Maria T; Weisburd, Ben; Won, Hong-Hee; Yu, Dongmei; Altshuler, David M; Ardissino, Diego; Boehnke, Michael; Danesh, John; Donnelly, Stacey; Elosua, Roberto; Florez, Jose C; Gabriel, Stacey B; Getz, Gad; Glatt, Stephen J; Hultman, Christina M; Kathiresan, Sekar; Laakso, Markku; McCarroll, Steven; McCarthy, Mark I; McGovern, Dermot; McPherson, Ruth; Neale, Benjamin M; Palotie, Aarno; Purcell, Shaun M; Saleheen, Danish; Scharf, Jeremiah M; Sklar, Pamela; Sullivan, Patrick F; Tuomilehto, Jaakko; Tsuang, Ming T; Watkins, Hugh C; Wilson, James G; Daly, Mark J; MacArthur, Daniel G

2016-08-18

Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human 'knockout' variants in protein-coding genes.

Design optimization of cold-formed steel portal frames taking into account the effect of building topology

NASA Astrophysics Data System (ADS)

Phan, Duoc T.; Lim, James B. P.; Sha, Wei; Siew, Calvin Y. M.; Tanyimboh, Tiku T.; Issa, Honar K.; Mohammad, Fouad A.

2013-04-01

Cold-formed steel portal frames are a popular form of construction for low-rise commercial, light industrial and agricultural buildings with spans of up to 20 m. In this article, a real-coded genetic algorithm is described that is used to minimize the cost of the main frame of such buildings. The key decision variables considered in this proposed algorithm consist of both the spacing and pitch of the frame as continuous variables, as well as the discrete section sizes. A routine taking the structural analysis and frame design for cold-formed steel sections is embedded into a genetic algorithm. The results show that the real-coded genetic algorithm handles effectively the mixture of design variables, with high robustness and consistency in achieving the optimum solution. All wind load combinations according to Australian code are considered in this research. Results for frames with knee braces are also included, for which the optimization achieved even larger savings in cost.

Non-coding RNAs' partitioning in the evolution of photosynthetic organisms via energy transduction and redox signaling.

PubMed

Kotakis, Christos

2015-01-01

Ars longa, vita brevis -Hippocrates Chloroplasts and mitochondria are genetically semi-autonomous organelles inside the plant cell. These constructions formed after endosymbiosis and keep evolving throughout the history of life. Experimental evidence is provided for active non-coding RNAs (ncRNAs) in these prokaryote-like structures, and a possible functional imprinting on cellular electrophysiology by those RNA entities is described. Furthermore, updated knowledge on RNA metabolism of organellar genomes uncovers novel inter-communication bridges with the nucleus. This class of RNA molecules is considered as a unique ontogeny which transforms their biological role as a genetic rheostat into a synchronous biochemical one that can affect the energetic charge and redox homeostasis inside cells. A hypothesis is proposed where such modulation by non-coding RNAs is integrated with genetic signals regulating gene transfer. The implications of this working hypothesis are discussed, with particular reference to ncRNAs involvement in the organellar and nuclear genomes evolution since their integrity is functionally coupled with redox signals in photosynthetic organisms.

GPU-accelerated simulations of isolated black holes

NASA Astrophysics Data System (ADS)

Lewis, Adam G. M.; Pfeiffer, Harald P.

2018-05-01

We present a port of the numerical relativity code SpEC which is capable of running on NVIDIA GPUs. Since this code must be maintained in parallel with SpEC itself, a primary design consideration is to perform as few explicit code changes as possible. We therefore rely on a hierarchy of automated porting strategies. At the highest level we use TLoops, a C++ library of our design, to automatically emit CUDA code equivalent to tensorial expressions written into C++ source using a syntax similar to analytic calculation. Next, we trace out and cache explicit matrix representations of the numerous linear transformations in the SpEC code, which allows these to be performed on the GPU using pre-existing matrix-multiplication libraries. We port the few remaining important modules by hand. In this paper we detail the specifics of our port, and present benchmarks of it simulating isolated black hole spacetimes on several generations of NVIDIA GPU.

Optimal sensor placement for spatial lattice structure based on genetic algorithms

NASA Astrophysics Data System (ADS)

Liu, Wei; Gao, Wei-cheng; Sun, Yi; Xu, Min-jian

2008-10-01

Optimal sensor placement technique plays a key role in structural health monitoring of spatial lattice structures. This paper considers the problem of locating sensors on a spatial lattice structure with the aim of maximizing the data information so that structural dynamic behavior can be fully characterized. Based on the criterion of optimal sensor placement for modal test, an improved genetic algorithm is introduced to find the optimal placement of sensors. The modal strain energy (MSE) and the modal assurance criterion (MAC) have been taken as the fitness function, respectively, so that three placement designs were produced. The decimal two-dimension array coding method instead of binary coding method is proposed to code the solution. Forced mutation operator is introduced when the identical genes appear via the crossover procedure. A computational simulation of a 12-bay plain truss model has been implemented to demonstrate the feasibility of the three optimal algorithms above. The obtained optimal sensor placements using the improved genetic algorithm are compared with those gained by exiting genetic algorithm using the binary coding method. Further the comparison criterion based on the mean square error between the finite element method (FEM) mode shapes and the Guyan expansion mode shapes identified by data-driven stochastic subspace identification (SSI-DATA) method are employed to demonstrate the advantage of the different fitness function. The results showed that some innovations in genetic algorithm proposed in this paper can enlarge the genes storage and improve the convergence of the algorithm. More importantly, the three optimal sensor placement methods can all provide the reliable results and identify the vibration characteristics of the 12-bay plain truss model accurately.

The Automated Instrumentation and Monitoring System (AIMS) reference manual

NASA Technical Reports Server (NTRS)

Yan, Jerry; Hontalas, Philip; Listgarten, Sherry

1993-01-01

Whether a researcher is designing the 'next parallel programming paradigm,' another 'scalable multiprocessor' or investigating resource allocation algorithms for multiprocessors, a facility that enables parallel program execution to be captured and displayed is invaluable. Careful analysis of execution traces can help computer designers and software architects to uncover system behavior and to take advantage of specific application characteristics and hardware features. A software tool kit that facilitates performance evaluation of parallel applications on multiprocessors is described. The Automated Instrumentation and Monitoring System (AIMS) has four major software components: a source code instrumentor which automatically inserts active event recorders into the program's source code before compilation; a run time performance-monitoring library, which collects performance data; a trace file animation and analysis tool kit which reconstructs program execution from the trace file; and a trace post-processor which compensate for data collection overhead. Besides being used as prototype for developing new techniques for instrumenting, monitoring, and visualizing parallel program execution, AIMS is also being incorporated into the run-time environments of various hardware test beds to evaluate their impact on user productivity. Currently, AIMS instrumentors accept FORTRAN and C parallel programs written for Intel's NX operating system on the iPSC family of multi computers. A run-time performance-monitoring library for the iPSC/860 is included in this release. We plan to release monitors for other platforms (such as PVM and TMC's CM-5) in the near future. Performance data collected can be graphically displayed on workstations (e.g. Sun Sparc and SGI) supporting X-Windows (in particular, Xl IR5, Motif 1.1.3).

ANT: Software for Generating and Evaluating Degenerate Codons for Natural and Expanded Genetic Codes.

PubMed

Engqvist, Martin K M; Nielsen, Jens

2015-08-21

The Ambiguous Nucleotide Tool (ANT) is a desktop application that generates and evaluates degenerate codons. Degenerate codons are used to represent DNA positions that have multiple possible nucleotide alternatives. This is useful for protein engineering and directed evolution, where primers specified with degenerate codons are used as a basis for generating libraries of protein sequences. ANT is intuitive and can be used in a graphical user interface or by interacting with the code through a defined application programming interface. ANT comes with full support for nonstandard, user-defined, or expanded genetic codes (translation tables), which is important because synthetic biology is being applied to an ever widening range of natural and engineered organisms. The Python source code for ANT is freely distributed so that it may be used without restriction, modified, and incorporated in other software or custom data pipelines.

Physical Model for the Evolution of the Genetic Code

NASA Astrophysics Data System (ADS)

Yamashita, Tatsuro; Narikiyo, Osamu

2011-12-01

Using the shape space of codons and tRNAs we give a physical description of the genetic code evolution on the basis of the codon capture and ambiguous intermediate scenarios in a consistent manner. In the lowest dimensional version of our description, a physical quantity, codon level is introduced. In terms of the codon levels two scenarios are typically classified into two different routes of the evolutional process. In the case of the ambiguous intermediate scenario we perform an evolutional simulation implemented cost selection of amino acids and confirm a rapid transition of the code change. Such rapidness reduces uncomfortableness of the non-unique translation of the code at intermediate state that is the weakness of the scenario. In the case of the codon capture scenario the survival against mutations under the mutational pressure minimizing GC content in genomes is simulated and it is demonstrated that cells which experience only neutral mutations survive.

Color-coding cancer and stromal cells with genetic reporters in a patient-derived orthotopic xenograft (PDOX) model of pancreatic cancer enhances fluorescence-guided surgery

PubMed Central

Yano, Shuya; Hiroshima, Yukihiko; Maawy, Ali; Kishimoto, Hiroyuki; Suetsugu, Atsushi; Miwa, Shinji; Toneri, Makoto; Yamamoto, Mako; Katz, Matthew H.G.; Fleming, Jason B.; Urata, Yasuo; Tazawa, Hiroshi; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M.

2015-01-01

Precise fluorescence-guided surgery (FGS) for pancreatic cancer has the potential to greatly improve the outcome in this recalcitrant disease. In order to achieve this goal, we have used genetic reporters to color code cancer and stroma cells in a patient-derived orthotopic xenograft (PDOX) model. The telomerase-dependent green fluorescent protein (GFP) containing adenovirus OBP401 was used to label the cancer cells of the pancreatic cancer PDOX. The PDOX was previously grown in a red fluorescent protein (RFP) transgenic mouse that stably labeled the PDOX stroma cells bright red. The color-coded PDOX model enabled FGS to completely resect the pancreatic tumors including stroma. Dual-colored FGS significantly prevented local recurrence, which bright-light surgery (BLS) or single color could not. FGS, with color-coded cancer and stroma cells has important potential for improving the outcome of recalcitrant cancer. PMID:26088297

Prenatal Genetic Testing Chart

MedlinePlus

... www.acog.org/Patients/FAQs/Prenatal-Genetic-Diagnostic-Tests › › Resources & Publications Committee Opinions Practice Bulletins Patient Education Green Journal Clinical Updates Practice Management Coding Health Info Technology Professional Liability Managing Your Practice Patient Safety & Quality ...

Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy

DTIC Science & Technology

2015-10-01

available, work will commence. Tau, genetics , susceptibility, MAPT, chronic traumatic encephalopathy, Alzheimer disease U U U U 1 USAMRMC Table of...AWARD NUMBER: W81XWH-14-1-0399 TITLE: Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy PRINCIPAL INVESTIGATOR: John F...Include area code) October 2015 Annual Report 30 Sep 2014 - 29 Sep 2015 Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy John

An integrated, structure- and energy-based view of the genetic code.

PubMed

Grosjean, Henri; Westhof, Eric

2016-09-30

The principles of mRNA decoding are conserved among all extant life forms. We present an integrative view of all the interaction networks between mRNA, tRNA and rRNA: the intrinsic stability of codon-anticodon duplex, the conformation of the anticodon hairpin, the presence of modified nucleotides, the occurrence of non-Watson-Crick pairs in the codon-anticodon helix and the interactions with bases of rRNA at the A-site decoding site. We derive a more information-rich, alternative representation of the genetic code, that is circular with an unsymmetrical distribution of codons leading to a clear segregation between GC-rich 4-codon boxes and AU-rich 2:2-codon and 3:1-codon boxes. All tRNA sequence variations can be visualized, within an internal structural and energy framework, for each organism, and each anticodon of the sense codons. The multiplicity and complexity of nucleotide modifications at positions 34 and 37 of the anticodon loop segregate meaningfully, and correlate well with the necessity to stabilize AU-rich codon-anticodon pairs and to avoid miscoding in split codon boxes. The evolution and expansion of the genetic code is viewed as being originally based on GC content with progressive introduction of A/U together with tRNA modifications. The representation we present should help the engineering of the genetic code to include non-natural amino acids. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Genomic profiles of low-grade murine gliomas evolve during progression to glioblastoma. | Office of Cancer Genomics

Cancer.gov

Background: Gliomas are diverse neoplasms with multiple molecular subtypes. How tumor-initiating mutations relate to molecular subtypes as these tumors evolve during malignant progression remains unclear.Methods: We used genetically engineered mouse models, histopathology, genetic lineage tracing, expression profiling, and copy number analyses to examine how genomic tumor diversity evolves during the course of malignant progression from low- to high-grade disease.

Rewiring protein synthesis: From natural to synthetic amino acids.

PubMed

Fan, Yongqiang; Evans, Christopher R; Ling, Jiqiang

2017-11-01

The protein synthesis machinery uses 22 natural amino acids as building blocks that faithfully decode the genetic information. Such fidelity is controlled at multiple steps and can be compromised in nature and in the laboratory to rewire protein synthesis with natural and synthetic amino acids. This review summarizes the major quality control mechanisms during protein synthesis, including aminoacyl-tRNA synthetases, elongation factors, and the ribosome. We will discuss evolution and engineering of such components that allow incorporation of natural and synthetic amino acids at positions that deviate from the standard genetic code. The protein synthesis machinery is highly selective, yet not fixed, for the correct amino acids that match the mRNA codons. Ambiguous translation of a codon with multiple amino acids or complete reassignment of a codon with a synthetic amino acid diversifies the proteome. Expanding the genetic code with synthetic amino acids through rewiring protein synthesis has broad applications in synthetic biology and chemical biology. Biochemical, structural, and genetic studies of the translational quality control mechanisms are not only crucial to understand the physiological role of translational fidelity and evolution of the genetic code, but also enable us to better design biological parts to expand the proteomes of synthetic organisms. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of Different Correlations on TRACEv4.160 Predicted Critical Heat Flux

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

Jasiulevicius, A.; Macian-Juan, R.

2006-07-01

This paper presents an independent assessment of the Critical Heat Flux (CHF) models implemented in TRACEv4.160 with data from the experiments carried out at the Royal Institute of Technology (RIT) in Stockholm, Sweden, with single vertical uniformly heated 7.0 m long tubes. In previous CHF assessment studies with TRACE, it was noted that, although the overall code predictions in long single tubes with inner diameters of 1.0 to 2.49 cm agreed rather well with the results of experiments (with r.m.s. error being 25.6%), several regions of pressure and coolant mass flux could be identified, in which the code strongly under-predictsmore » or over-predicts the CHF. In order to evaluate the possibility of improving the code performance, some of the most widely used and assessed CHF correlations were additionally implemented in TRACEv4.160, namely Bowring, Levitan - Lantsman, and Tong-W3. The results obtained for the CHF predictions in single tubes with uniform axial heat flux by using these correlations, were compared to the results produced with the standard TRACE correlations (Biasi and CISE-GE), and with the experimental data from RIT, which covered a broad range of pressures (3-20 MPa) and coolant mass fluxes (500-3000 kg/m{sup 2}s). Several hundreds of experimental points were calculated to cover the parameter range mentioned above for the evaluation of the newly implemented correlations in the TRACEv4.160 code. (author)« less

[Assisted reproduction and artificial insemination and genetic manipulation in the Criminal Code of the Federal District, Mexico].

PubMed

Brena Sesma, Ingrid

2004-01-01

The article that one presents has for purpose outline and comment on the recent modifications to the Penal Code for the Federal District of México which establish, for the first time, crimes related to the artificial procreation and to the genetic manipulation. Also one refers to the interaction of the new legal texts with the sanitary legislation of the country. Since it will be stated in some cases they present confrontations between the penal and the sanitary reglamentation and some points related to the legality or unlawfulness of a conduct that stayed without the enough development. These lacks will complicate the application of the new rules of the Penal Code of the Federal District.

Using AORSA to simulate helicon waves in DIII-D

NASA Astrophysics Data System (ADS)

Lau, C.; Jaeger, E. F.; Bertelli, N.; Berry, L. A.; Blazevski, D.; Green, D. L.; Murakami, M.; Park, J. M.; Pinsker, R. I.; Prater, R.

2015-12-01

Recent efforts have shown that helicon waves (fast waves at > 20ωci) may be an attractive option for driving efficient off-axis current drive during non-inductive tokamak operation for DIII-D, ITER and DEMO. For DIII-D scenarios, the ray tracing code, GENRAY, has been extensively used to study helicon current drive efficiency and location as a function of many plasma parameters. The full wave code, AORSA, which is applicable to arbitrary Larmor radius and can resolve arbitrary ion cyclotron harmonic order, has been recently used to validate the ray tracing technique at these high cyclotron harmonics. If the SOL is ignored, it will be shown that the GENRAY and AORSA calculated current drive profiles are comparable for the envisioned high beta advanced scenarios for DIII-D, where there is high single pass absorption due to electron Landau damping and minimal ion damping. AORSA is also been used to estimate possible SOL effects on helicon current drive coupling and SOL absorption due to collisional and slow wave effects.

Standardisation of the (129)I, (151)Sm and (166m)Ho activity concentration using the CIEMAT/NIST efficiency tracing method.

PubMed

Altzitzoglou, Timotheos; Rožkov, Andrej

2016-03-01

The (129)I, (151)Sm and (166m)Ho standardisations using the CIEMAT/NIST efficiency tracing method, that have been carried out in the frame of the European Metrology Research Program project "Metrology for Radioactive Waste Management" are described. The radionuclide beta counting efficiencies were calculated using two computer codes CN2005 and MICELLE2. The sensitivity analysis of the code input parameters (ionization quenching factor, beta shape factor) on the calculated efficiencies was performed, and the results are discussed. The combined relative standard uncertainty of the standardisations of the (129)I, (151)Sm and (166m)Ho solutions were 0.4%, 0.5% and 0.4%, respectively. The stated precision obtained using the CIEMAT/NIST method is better than that previously reported in the literature obtained by the TDCR ((129)I), the 4πγ-NaI ((166m)Ho) counting or the CIEMAT/NIST method ((151)Sm). Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Moral codes of mothering and the introduction of welfare-to-work in Ontario.

PubMed

Gazso, Amber

2012-02-01

In this paper, I trace how the reform of social assistance in Ontario, especially the post-1990s enforcement of lone mothers' employability via welfare-to-work programs, parallels shifts in dominant moral codes of mothering, from "mother-carer" to "mother-worker." Additionally, I use this case as an entry point to consider the implications of public and policy allegiance to these moral codes for all mothers. The central argument I make is that the introduction of welfare-to-work programs in Ontario did not occur in a neoliberal state-sanctioned vacuum but also involved the circulation of ideas about moral mothering outside of policy into policy.

An update on the BQCD Hybrid Monte Carlo program

NASA Astrophysics Data System (ADS)

Haar, Taylor Ryan; Nakamura, Yoshifumi; Stüben, Hinnerk

2018-03-01

We present an update of BQCD, our Hybrid Monte Carlo program for simulating lattice QCD. BQCD is one of the main production codes of the QCDSF collaboration and is used by CSSM and in some Japanese finite temperature and finite density projects. Since the first publication of the code at Lattice 2010 the program has been extended in various ways. New features of the code include: dynamical QED, action modification in order to compute matrix elements by using Feynman-Hellman theory, more trace measurements (like Tr(D-n) for K, cSW and chemical potential reweighting), a more flexible integration scheme, polynomial filtering, term-splitting for RHMC, and a portable implementation of performance critical parts employing SIMD.

A genetic code Boolean structure. II. The genetic information system as a Boolean information system.

PubMed

Sanchez, Robersy; Grau, Ricardo

2005-09-01

A Boolean structure of the genetic code where Boolean deductions have biological and physicochemical meanings was discussed in a previous paper. Now, from these Boolean deductions we propose to define the value of amino acid information in order to consider the genetic information system as a communication system and to introduce the semantic content of information ignored by the conventional information theory. In this proposal, the value of amino acid information is proportional to the molecular weight of amino acids with a proportional constant of about 1.96 x 10(25) bits per kg. In addition to this, for the experimental estimations of the minimum energy dissipation in genetic logic operations, we present two postulates: (1) the energy Ei (i=1,2,...,20) of amino acids in the messages conveyed by proteins is proportional to the value of information, and (2) amino acids are distributed according to their energy Ei so the amino acid population in proteins follows a Boltzmann distribution. Specifically, in the genetic message carried by the DNA from the genomes of living organisms, we found that the minimum energy dissipation in genetic logic operations was close to kTLn(2) joules per bit.

TOMO3D: 3-D joint refraction and reflection traveltime tomography parallel code for active-source seismic data—synthetic test

NASA Astrophysics Data System (ADS)

Meléndez, A.; Korenaga, J.; Sallarès, V.; Miniussi, A.; Ranero, C. R.

2015-10-01

We present a new 3-D traveltime tomography code (TOMO3D) for the modelling of active-source seismic data that uses the arrival times of both refracted and reflected seismic phases to derive the velocity distribution and the geometry of reflecting boundaries in the subsurface. This code is based on its popular 2-D version TOMO2D from which it inherited the methods to solve the forward and inverse problems. The traveltime calculations are done using a hybrid ray-tracing technique combining the graph and bending methods. The LSQR algorithm is used to perform the iterative regularized inversion to improve the initial velocity and depth models. In order to cope with an increased computational demand due to the incorporation of the third dimension, the forward problem solver, which takes most of the run time (˜90 per cent in the test presented here), has been parallelized with a combination of multi-processing and message passing interface standards. This parallelization distributes the ray-tracing and traveltime calculations among available computational resources. The code's performance is illustrated with a realistic synthetic example, including a checkerboard anomaly and two reflectors, which simulates the geometry of a subduction zone. The code is designed to invert for a single reflector at a time. A data-driven layer-stripping strategy is proposed for cases involving multiple reflectors, and it is tested for the successive inversion of the two reflectors. Layers are bound by consecutive reflectors, and an initial velocity model for each inversion step incorporates the results from previous steps. This strategy poses simpler inversion problems at each step, allowing the recovery of strong velocity discontinuities that would otherwise be smoothened.

Imaging genetics and the neurobiological basis of individual differences in vulnerability to addiction.

PubMed

Sweitzer, Maggie M; Donny, Eric C; Hariri, Ahmad R

2012-06-01

Addictive disorders are heritable, but the search for candidate functional polymorphisms playing an etiological role in addiction is hindered by complexity of the phenotype and the variety of factors interacting to impact behavior. Advances in human genome sequencing and neuroimaging technology provide an unprecedented opportunity to explore the impact of functional genetic variants on variability in behaviorally relevant neural circuitry. Here, we present a model for merging these technologies to trace the links between genes, brain, and addictive behavior. We describe imaging genetics and discuss the utility of its application to addiction. We then review data pertaining to impulsivity and reward circuitry as an example of how genetic variation may lead to variation in behavioral phenotype. Finally, we present preliminary data relating the neural basis of reward processing to individual differences in nicotine dependence. Complex human behaviors such as addiction can be traced to their basic genetic building blocks by identifying intermediate behavioral phenotypes, associated neural circuitry, and underlying molecular signaling pathways. Impulsivity has been linked with variation in reward-related activation in the ventral striatum (VS), altered dopamine signaling, and functional polymorphisms of DRD2 and DAT1 genes. In smokers, changes in reward-related VS activation induced by smoking abstinence may be associated with severity of nicotine dependence. Variation in genes related to dopamine signaling may contribute to heterogeneity in VS sensitivity to reward and, ultimately, to addiction. These findings illustrate the utility of the imaging genetics approach for investigating the neurobiological basis for vulnerability to addiction. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Decoding the non-coding genome: elucidating genetic risk outside the coding genome.

PubMed

Barr, C L; Misener, V L

2016-01-01

Current evidence emerging from genome-wide association studies indicates that the genetic underpinnings of complex traits are likely attributable to genetic variation that changes gene expression, rather than (or in combination with) variation that changes protein-coding sequences. This is particularly compelling with respect to psychiatric disorders, as genetic changes in regulatory regions may result in differential transcriptional responses to developmental cues and environmental/psychosocial stressors. Until recently, however, the link between transcriptional regulation and psychiatric genetic risk has been understudied. Multiple obstacles have contributed to the paucity of research in this area, including challenges in identifying the positions of remote (distal from the promoter) regulatory elements (e.g. enhancers) and their target genes and the underrepresentation of neural cell types and brain tissues in epigenome projects - the availability of high-quality brain tissues for epigenetic and transcriptome profiling, particularly for the adolescent and developing brain, has been limited. Further challenges have arisen in the prediction and testing of the functional impact of DNA variation with respect to multiple aspects of transcriptional control, including regulatory-element interaction (e.g. between enhancers and promoters), transcription factor binding and DNA methylation. Further, the brain has uncommon DNA-methylation marks with unique genomic distributions not found in other tissues - current evidence suggests the involvement of non-CG methylation and 5-hydroxymethylation in neurodevelopmental processes but much remains unknown. We review here knowledge gaps as well as both technological and resource obstacles that will need to be overcome in order to elucidate the involvement of brain-relevant gene-regulatory variants in genetic risk for psychiatric disorders. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Genetics and culture: the geneticization thesis.

PubMed

ten Have, H A

2001-01-01

The concept of 'geneticization' has been introduced in the scholarly literature to describe the various interlocking and imperceptible mechanisms of interaction between medicine, genetics, society and culture. It is argued that Western culture currently is deeply involved in a process of geneticization. This process implies a redefinition of individuals in terms of DNA codes, a new language to describe and interpret human life and behavior in a genomic vocabulary of codes, blueprints, traits, dispositions, genetic mapping, and a gentechnological approach to disease, health and the body. This article analyses the thesis of 'geneticization'. Explaining the implications of the thesis, and discussing the critical refutations, it is argued that 'geneticization' primarily is a heuristic tool that can help to re-focus the moral debate on the implications of new genetic knowledge towards interpersonal relations, the power of medicine, the cultural context and social constraints, rather than emphasizing issues as personal autonomy and individual rights.

Parallelizing serial code for a distributed processing environment with an application to high frequency electromagnetic scattering

NASA Astrophysics Data System (ADS)

Work, Paul R.

1991-12-01

This thesis investigates the parallelization of existing serial programs in computational electromagnetics for use in a parallel environment. Existing algorithms for calculating the radar cross section of an object are covered, and a ray-tracing code is chosen for implementation on a parallel machine. Current parallel architectures are introduced and a suitable parallel machine is selected for the implementation of the chosen ray-tracing algorithm. The standard techniques for the parallelization of serial codes are discussed, including load balancing and decomposition considerations, and appropriate methods for the parallelization effort are selected. A load balancing algorithm is modified to increase the efficiency of the application, and a high level design of the structure of the serial program is presented. A detailed design of the modifications for the parallel implementation is also included, with both the high level and the detailed design specified in a high level design language called UNITY. The correctness of the design is proven using UNITY and standard logic operations. The theoretical and empirical results show that it is possible to achieve an efficient parallel application for a serial computational electromagnetic program where the characteristics of the algorithm and the target architecture critically influence the development of such an implementation.

Decoding the genome with an integrative analysis tool: combinatorial CRM Decoder.

PubMed

Kang, Keunsoo; Kim, Joomyeong; Chung, Jae Hoon; Lee, Daeyoup

2011-09-01

The identification of genome-wide cis-regulatory modules (CRMs) and characterization of their associated epigenetic features are fundamental steps toward the understanding of gene regulatory networks. Although integrative analysis of available genome-wide information can provide new biological insights, the lack of novel methodologies has become a major bottleneck. Here, we present a comprehensive analysis tool called combinatorial CRM decoder (CCD), which utilizes the publicly available information to identify and characterize genome-wide CRMs in a species of interest. CCD first defines a set of the epigenetic features which is significantly associated with a set of known CRMs as a code called 'trace code', and subsequently uses the trace code to pinpoint putative CRMs throughout the genome. Using 61 genome-wide data sets obtained from 17 independent mouse studies, CCD successfully catalogued ∼12 600 CRMs (five distinct classes) including polycomb repressive complex 2 target sites as well as imprinting control regions. Interestingly, we discovered that ∼4% of the identified CRMs belong to at least two different classes named 'multi-functional CRM', suggesting their functional importance for regulating spatiotemporal gene expression. From these examples, we show that CCD can be applied to any potential genome-wide datasets and therefore will shed light on unveiling genome-wide CRMs in various species.

Students' Views and Attitudes Towards the Communication Code Used in Press Articles About Science

NASA Astrophysics Data System (ADS)

Halkia, Krystallia; Mantzouridis, Dimitris

2005-10-01

The present research was designed to investigate the reaction of secondary school students to the communication code that the press uses in science articles: it attempts to trace which communication techniques can be of potential use in science education. The sample of the research consists of 351 secondary school students. The research instrument is a questionnaire, which attempts to trace students’ preferences regarding newspaper science articles, to explore students’ attitudes towards the science articles published in the press and to investigate students’ reactions towards four newspaper science articles. These articles deal with different aspects of science and reflect different communication strategies. The results of the research reveal that secondary school students view the communication codes used in press science articles as being more interesting and comprehensible than those of their science textbooks. Predominantly, they do not select science articles that present their data in a scientific way (diagrams and abstract graphs). On the contrary, they do select science articles and passages in them, which use an emotional/‘poetic’ language with a lot of metaphors and analogies to introduce complex science concepts. It also seems that the narrative elements found in popularized science articles attract students’ interest and motivate them towards further reading.

Metabolically Generated Stable Isotope-Labeled Deoxynucleoside Code for Tracing DNA N6-Methyladenine in Human Cells.

PubMed

Liu, Baodong; Liu, Xiaoling; Lai, Weiyi; Wang, Hailin

2017-06-06

DNA N 6 -methyl-2'-deoxyadenosine (6mdA) is an epigenetic modification in both eukaryotes and bacteria. Here we exploited stable isotope-labeled deoxynucleoside [ 15 N 5 ]-2'-deoxyadenosine ([ 15 N 5 ]-dA) as an initiation tracer and for the first time developed a metabolically differential tracing code for monitoring DNA 6mdA in human cells. We demonstrate that the initiation tracer [ 15 N 5 ]-dA undergoes a specific and efficient adenine deamination reaction leading to the loss the exocyclic amine 15 N, and further utilizes the purine salvage pathway to generate mainly both [ 15 N 4 ]-dA and [ 15 N 4 ]-2'-deoxyguanosine ([ 15 N 4 ]-dG) in mammalian genomes. However, [ 15 N 5 ]-dA is largely retained in the genomes of mycoplasmas, which are often found in cultured cells and experimental animals. Consequently, the methylation of dA generates 6mdA with a consistent coding pattern, with a predominance of [ 15 N 4 ]-6mdA. Therefore, mammalian DNA 6mdA can be potentially discriminated from that generated by infecting mycoplasmas. Collectively, we show a promising approach for identification of authentic DNA 6mdA in human cells and determine if the human cells are contaminated with mycoplasmas.

Genetically improved BarraCUDA.

PubMed

Langdon, W B; Lam, Brian Yee Hong

2017-01-01

BarraCUDA is an open source C program which uses the BWA algorithm in parallel with nVidia CUDA to align short next generation DNA sequences against a reference genome. Recently its source code was optimised using "Genetic Improvement". The genetically improved (GI) code is up to three times faster on short paired end reads from The 1000 Genomes Project and 60% more accurate on a short BioPlanet.com GCAT alignment benchmark. GPGPU BarraCUDA running on a single K80 Tesla GPU can align short paired end nextGen sequences up to ten times faster than bwa on a 12 core server. The speed up was such that the GI version was adopted and has been regularly downloaded from SourceForge for more than 12 months.

Emotional expressions in voice and music: same code, same effect?

PubMed

Escoffier, Nicolas; Zhong, Jidan; Schirmer, Annett; Qiu, Anqi

2013-08-01

Scholars have documented similarities in the way voice and music convey emotions. By using functional magnetic resonance imaging (fMRI) we explored whether these similarities imply overlapping processing substrates. We asked participants to trace changes in either the emotion or pitch of vocalizations and music using a joystick. Compared to music, vocalizations more strongly activated superior and middle temporal cortex, cuneus, and precuneus. However, despite these differences, overlapping rather than differing regions emerged when comparing emotion with pitch tracing for music and vocalizations, respectively. Relative to pitch tracing, emotion tracing activated medial superior frontal and anterior cingulate cortex regardless of stimulus type. Additionally, we observed emotion specific effects in primary and secondary auditory cortex as well as in medial frontal cortex that were comparable for voice and music. Together these results indicate that similar mechanisms support emotional inferences from vocalizations and music and that these mechanisms tap on a general system involved in social cognition. Copyright © 2011 Wiley Periodicals, Inc.

Helping Couples Fulfill the "Highest of Life's Goals": Mate Selection, Marriage Counselling, and Genetic Counseling in United States.

PubMed

Stillwell, Devon

2016-02-01

This article traces the history of modern genetic counseling to mate selection and marriage counselling practices of the early-20th century. Mate selection revolved around a belief that human heredity could be improved and genetic diseases eradicated through better breeding. Marriage counselling, though interested in reproduction, was also concerned with the emotional and psychological well-being of couples. These two practices coalesced most obviously in the work of well-known geneticist Sheldon Reed. Even as marriage and genetic counselling diverged in the post-WWII period, vestiges of these practices remain in contemporary counseling experiences with family planning and genetic screening programs. Emphasizing points of continuity between "positive" eugenic ideologies and modern genetic practices elaborates the diverse origins of genetic counseling. It also exposes how genetic counselors have become involved in genetic enterprises beyond standard clinical settings, and prods at key issues in the interaction between genetic science and social values.

Effective algorithm for ray-tracing simulations of lobster eye and similar reflective optical systems

NASA Astrophysics Data System (ADS)

Tichý, Vladimír; Hudec, René; Němcová, Šárka

2016-06-01

The algorithm presented is intended mainly for lobster eye optics. This type of optics (and some similar types) allows for a simplification of the classical ray-tracing procedure that requires great many rays to simulate. The method presented performs the simulation of a only few rays; therefore it is extremely effective. Moreover, to simplify the equations, a specific mathematical formalism is used. Only a few simple equations are used, therefore the program code can be simple as well. The paper also outlines how to apply the method to some other reflective optical systems.

tRNA acceptor-stem and anticodon bases embed separate features of amino acid chemistry

PubMed Central

Carter, Charles W.; Wolfenden, Richard

2016-01-01

abstract The universal genetic code is a translation table by which nucleic acid sequences can be interpreted as polypeptides with a wide range of biological functions. That information is used by aminoacyl-tRNA synthetases to translate the code. Moreover, amino acid properties dictate protein folding. We recently reported that digital correlation techniques could identify patterns in tRNA identity elements that govern recognition by synthetases. Our analysis, and the functionality of truncated synthetases that cannot recognize the tRNA anticodon, support the conclusion that the tRNA acceptor stem houses an independent code for the same 20 amino acids that likely functioned earlier in the emergence of genetics. The acceptor-stem code, related to amino acid size, is distinct from a code in the anticodon that is related to amino acid polarity. Details of the acceptor-stem code suggest that it was useful in preserving key properties of stereochemically-encoded peptides that had developed the capacity to interact catalytically with RNA. The quantitative embedding of the chemical properties of amino acids into tRNA bases has implications for the origins of molecular biology. PMID:26595350

Origin of enormous trace metal enrichments in weathering mantles of Jurassic carbonates: evidence from Sr, Nd and Pb isotopes

NASA Astrophysics Data System (ADS)

Hissler, C.; Stille, P.; Juilleret, J.; Iffly, J.; Perrone, T.; Morvan, G.

2013-12-01

Weathering mantels are widespread worldwide and include lateritic, sandy and kaolinite-rich saprolites and residuals of partially dissolved carbonate rocks. These old regolith systems have a complex history of formation and may present a polycyclic evolution due to successive geological and pedogenetic processes that affected the profile. Until now, only few studies highlighted the unusual content of associated trace elements in this type of weathering mantle. For instance, these enrichments can represent about five times the content of the underlying Bajocian to Oxfordian limestone/marl complexes, which have been relatively poorly studied compared to weathering mantle developed on magmatic bedrocks. Up to now, neither soil, nor saprolite formation has to our knowledge been geochemically elucidated. Therefore, the aim of this study was to examine more closely the soil forming dynamics and the relationship of the chemical soil composition to potential sources (saprolite, Bajocian silty marls and limestones, atmospheric particles deposition...). Of special interest has also been the origin of trace metals and the processes causing their enrichments. Especially Rare Earth Element (REE) distribution patterns and Sr, Nd and Pb isotope ratios are particularly well suited to identify trace element migration, to recognize origin and mixing processes and, in addition, to decipher possible anthropogenic and/or "natural" atmosphere-derived contributions to the soil. Moreover, leaching experiments shall help to identify mobile phases in the soil system. This may inform on the stability of trace elements and especially on their behaviour in these Fe-enriched carbonate systems. Trace metal migration and enrichments were studied on a cambisol developing on an underlying Jurassic limestone. The base is strongly enriched among others in rare earth elements (ΣREE: 2640ppm) or redox-sensitive elements such as Fe (44 wt.%), V (920ppm), Cr (700ppm), Zn (550ppm), As (260ppm), Co (45ppm) and Cd (2.4ppm). The underlying limestone and marl show, compared to average world carbonates, enrichments in the same elements and trace element distribution patterns similar to the soil suggesting their close genetic relationship. Pb, Sr and Nd isotope data allow to identify three principal components in the soil: a silicate-rich phase at close to the surface, a strongly trace metal enriched component at the bottom of the soil profile and an anthropogenic, atmosphere- derived component detected in the soil leachates. The isotopic mixing curves defined by the soil samples point to the close genetic connection between upper and lowermost soil horizons. The Nd isotopic composition of the leachates of all soil horizons are in contrast to the untreated soil and residual soil samples very homogeneous suggesting that the leachable phases of the upper and lower soil horizons are genetically connected. The downward migration of the trace metals is stopped at this soil level due to the presence of important secondary calcite precipitations, smectite and Fe-oxide accumulations. Mass balance calculations indicate that the enrichment process goes along with a volume increase relative to the bottom soil horizons.

FormTracer. A mathematica tracing package using FORM

NASA Astrophysics Data System (ADS)

Cyrol, Anton K.; Mitter, Mario; Strodthoff, Nils

2017-10-01

We present FormTracer, a high-performance, general purpose, easy-to-use Mathematica tracing package which uses FORM. It supports arbitrary space and spinor dimensions as well as an arbitrary number of simple compact Lie groups. While keeping the usability of the Mathematica interface, it relies on the efficiency of FORM. An additional performance gain is achieved by a decomposition algorithm that avoids redundant traces in the product tensors spaces. FormTracer supports a wide range of syntaxes which endows it with a high flexibility. Mathematica notebooks that automatically install the package and guide the user through performing standard traces in space-time, spinor and gauge-group spaces are provided. Program Files doi:http://dx.doi.org/10.17632/7rd29h4p3m.1 Licensing provisions: GPLv3 Programming language: Mathematica and FORM Nature of problem: Efficiently compute traces of large expressions Solution method: The expression to be traced is decomposed into its subspaces by a recursive Mathematica expansion algorithm. The result is subsequently translated to a FORM script that takes the traces. After FORM is executed, the final result is either imported into Mathematica or exported as optimized C/C++/Fortran code. Unusual features: The outstanding features of FormTracer are the simple interface, the capability to efficiently handle an arbitrary number of Lie groups in addition to Dirac and Lorentz tensors, and a customizable input-syntax.

The Coding of Biological Information: From Nucleotide Sequence to Protein Recognition

NASA Astrophysics Data System (ADS)

Štambuk, Nikola

The paper reviews the classic results of Swanson, Dayhoff, Grantham, Blalock and Root-Bernstein, which link genetic code nucleotide patterns to the protein structure, evolution and molecular recognition. Symbolic representation of the binary addresses defining particular nucleotide and amino acid properties is discussed, with consideration of: structure and metric of the code, direct correspondence between amino acid and nucleotide information, and molecular recognition of the interacting protein motifs coded by the complementary DNA and RNA strands.

Calcium, potassium, iron, copper and zinc concentrations in the white and gray matter of the cerebellum and corpus callosum in brain of four genetic mouse strains

NASA Astrophysics Data System (ADS)

Sergeant, C.; Vesvres, M. H.; Devès, G.; Guillou, F.

2005-04-01

In the central nervous system, metallic cations are involved in oligodendrocyte maturation and myelinogenesis. Moreover, the metallic cations have been associated with pathogenesis, particularly multiple sclerosis and malignant gliomas. The brain is vulnerable to either a deficit or an excess of available trace elements. Relationship between trace metals and myelinogenesis is important in understanding a severe human pathology : the multiple sclerosis, which remains without efficient treatment. One approach to understand this disease has used mutant or transgenic mice presenting myelin deficiency or excess. But to date, the concentration of trace metals and mineral elements in white and gray matter areas in wild type brain is unknown. The aim of this study is to establish the reference concentrations of trace metals (iron, copper and zinc) and minerals (potassium and calcium) in the white and gray matter of the mouse cerebellum and corpus callosum. The brains of four different genetic mouse strains (C57Black6/SJL, C57Black6/D2, SJL and C3H) were analyzed. The freeze-dried samples were prepared to allow PIXE (Proton-induced X-ray emission) and RBS (Rutherford backscattering spectrometry) analyses with the nuclear microprobe in Bordeaux. The results obtained give the first reference values. Furthermore, one species out of the fours testes exhibited differences in calcium, iron and zinc concentrations in the white matter.

Analysis of Molecular Genetics Content in Spanish Secondary School Textbooks

ERIC Educational Resources Information Center

Martinez-Gracia, M. V.; Gil-Quilez, M. J.; Osada, J.

2006-01-01

The treatment of molecular biology in thirty-four Spanish high school biology textbooks has been analysed using a check-list made up of twenty-three items. The study showed a tendency to confuse the genetic code with genetic information. The treatment of DNA transcription, regulation of gene expression and translation were presented as masses of…

A field release of genetically engineered gypsy moth (Lymantria dispar L.) Nuclear Polyhedrosis Virus (LdNPV)

Treesearch

Vincent D' Amico; Joseph S. Elkinton; John D. Podgwaite; James M. Slavicek; Michael L. McManus; John P. Burand

1999-01-01

The gypsy moth (Lymantria dispar L.) nuclear polyhedrosis virus was genetically engineered for nonpersistence by removal of the gene coding for polyhedrin production and stabilized using a coocclusion process. A β-galactosidase marker gene was inserted into the genetically engineered virus (LdGEV) so that infected larvae could be tested for...

Length and nucleotide sequence polymorphism at the trnL and trnF non-coding regions of chloroplast genomes among Saccharum and Erianthus species

USDA-ARS?s Scientific Manuscript database

The aneupolyploidy genome of sugarcane (Saccharum hybrids spp.) and lack of a classical genetic linkage map make genetics research most difficult for sugarcane. Whole genome sequencing and genetic characterization of sugarcane and related taxa are far behind other crops. In this study, universal PCR...

BioQ: tracing experimental origins in public genomic databases using a novel data provenance model.

PubMed

Saccone, Scott F; Quan, Jiaxi; Jones, Peter L

2012-04-15

Public genomic databases, which are often used to guide genetic studies of human disease, are now being applied to genomic medicine through in silico integrative genomics. These databases, however, often lack tools for systematically determining the experimental origins of the data. We introduce a new data provenance model that we have implemented in a public web application, BioQ, for assessing the reliability of the data by systematically tracing its experimental origins to the original subjects and biologics. BioQ allows investigators to both visualize data provenance as well as explore individual elements of experimental process flow using precise tools for detailed data exploration and documentation. It includes a number of human genetic variation databases such as the HapMap and 1000 Genomes projects. BioQ is freely available to the public at http://bioq.saclab.net.

Shannon information entropy in the canonical genetic code.

PubMed

Nemzer, Louis R

2017-02-21

The Shannon entropy measures the expected information value of messages. As with thermodynamic entropy, the Shannon entropy is only defined within a system that identifies at the outset the collections of possible messages, analogous to microstates, that will be considered indistinguishable macrostates. This fundamental insight is applied here for the first time to amino acid alphabets, which group the twenty common amino acids into families based on chemical and physical similarities. To evaluate these schemas objectively, a novel quantitative method is introduced based the inherent redundancy in the canonical genetic code. Each alphabet is taken as a separate system that partitions the 64 possible RNA codons, the microstates, into families, the macrostates. By calculating the normalized mutual information, which measures the reduction in Shannon entropy, conveyed by single nucleotide messages, groupings that best leverage this aspect of fault tolerance in the code are identified. The relative importance of properties related to protein folding - like hydropathy and size - and function, including side-chain acidity, can also be estimated. This approach allows the quantification of the average information value of nucleotide positions, which can shed light on the coevolution of the canonical genetic code with the tRNA-protein translation mechanism. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Binotti, M.; Zhu, G.; Gray, A.

An analytical approach, as an extension of one newly developed method -- First-principle OPTical Intercept Calculation (FirstOPTIC) -- is proposed to treat the geometrical impact of three-dimensional (3-D) effects on parabolic trough optical performance. The mathematical steps of this analytical approach are presented and implemented numerically as part of the suite of FirstOPTIC code. In addition, the new code has been carefully validated against ray-tracing simulation results and available numerical solutions. This new analytical approach to treating 3-D effects will facilitate further understanding and analysis of the optical performance of trough collectors as a function of incidence angle.

Social Behavior in Medulloblastoma: Functional Analysis of Tumor-Supporting Glial Cells

DTIC Science & Technology

2015-10-01

GNPs are unipotent and only give rise to granule neurons. However, using MADM, a mouse genetic mosaic model, we found that medulloblastoma contain...demonstrated that GNPs are unipotent and only give rise to granule neurons. However, using MADM, a mouse genetic mosaic model with lineage tracing capability...UVa Animal Care and Use Committee, and got the approval. We then submitted ACURO documents and IACUC approval by UVa to USAMRMC Office of Research

Laboratory specimens and genetic privacy: evolution of legal theory.

PubMed

Lewis, Michelle Huckaby

2013-03-01

Although laboratory specimens are an important resource for biomedical research, controversy has arisen when research has been conducted without the knowledge or consent of the individuals who were the source of the specimens. This paper summarizes the most important litigation regarding the research use of laboratory specimens and traces the evolution of legal theory from property claims to claims related to genetic privacy interests. © 2013 American Society of Law, Medicine & Ethics, Inc.

Genetic association studies in β-hemoglobinopathies.

PubMed

Thein, Swee Lay

2013-01-01

Characterization of the molecular basis of the β-thalassemias and sickle cell disease (SCD) clearly showed that individuals with the same β-globin genotypes can have extremely diverse clinical severity. Two key modifiers, an innate ability to produce fetal hemoglobin and coinheritance of α-thalassemia, both derived from family and population studies, affect the pathophysiology of both disorders at the primary level. In the past 2 decades, scientific research had applied genetic approaches to identify additional genetic modifiers. The review summarizes recent genetic studies and key genetic modifiers identified and traces the story of fetal hemoglobin genetics, which has led to an emerging network of globin gene regulation. The discoveries have provided insights on new targets for therapeutic intervention and raise possibilities of developing fetal hemoglobin predictive diagnostics for predicting disease severity in the newborn and for integration into prenatal diagnosis to better inform genetic counseling.

FitSKIRT: genetic algorithms to automatically fit dusty galaxies with a Monte Carlo radiative transfer code

NASA Astrophysics Data System (ADS)

De Geyter, G.; Baes, M.; Fritz, J.; Camps, P.

2013-02-01

We present FitSKIRT, a method to efficiently fit radiative transfer models to UV/optical images of dusty galaxies. These images have the advantage that they have better spatial resolution compared to FIR/submm data. FitSKIRT uses the GAlib genetic algorithm library to optimize the output of the SKIRT Monte Carlo radiative transfer code. Genetic algorithms prove to be a valuable tool in handling the multi- dimensional search space as well as the noise induced by the random nature of the Monte Carlo radiative transfer code. FitSKIRT is tested on artificial images of a simulated edge-on spiral galaxy, where we gradually increase the number of fitted parameters. We find that we can recover all model parameters, even if all 11 model parameters are left unconstrained. Finally, we apply the FitSKIRT code to a V-band image of the edge-on spiral galaxy NGC 4013. This galaxy has been modeled previously by other authors using different combinations of radiative transfer codes and optimization methods. Given the different models and techniques and the complexity and degeneracies in the parameter space, we find reasonable agreement between the different models. We conclude that the FitSKIRT method allows comparison between different models and geometries in a quantitative manner and minimizes the need of human intervention and biasing. The high level of automation makes it an ideal tool to use on larger sets of observed data.

Tragedy or success? Elisabeth Goldschmidt (1912-1970) and genetics in Israel.

PubMed

Kirsh, Nurit

2013-06-01

This article introduces the reader to the life and work of Elisabeth Goldschmidt, the founding mother of the field of genetics in Israel. It concurrently strives to uncover the roots and development of genetics in Israel, tracing the crucial transition from classical Drosophila genetics to human genetics and the shift from a Germanic tradition of scientific research to an American one. Goldschmidt's personal biography is inextricably linked to the early stages of genetic research in Israel. The narrative of her life could have been a heroic and inspiring account of a female scientist who 'had it all', had its end been less tragic. Nevertheless, her life was rich, including a path of achievement and trail-blazing coupled with the joy and satisfaction she gleaned from her scientific work. Copyright © 2012 Elsevier Ltd. All rights reserved.

The generation of meaningful information in molecular systems.

PubMed

Wills, Peter R

2016-03-13

The physico-chemical processes occurring inside cells are under the computational control of genetic (DNA) and epigenetic (internal structural) programming. The origin and evolution of genetic information (nucleic acid sequences) is reasonably well understood, but scant attention has been paid to the origin and evolution of the molecular biological interpreters that give phenotypic meaning to the sequence information that is quite faithfully replicated during cellular reproduction. The near universality and age of the mapping from nucleotide triplets to amino acids embedded in the functionality of the protein synthetic machinery speaks to the early development of a system of coding which is still extant in every living organism. We take the origin of genetic coding as a paradigm of the emergence of computation in natural systems, focusing on the requirement that the molecular components of an interpreter be synthesized autocatalytically. Within this context, it is seen that interpreters of increasing complexity are generated by series of transitions through stepped dynamic instabilities (non-equilibrium phase transitions). The early phylogeny of the amino acyl-tRNA synthetase enzymes is discussed in such terms, leading to the conclusion that the observed optimality of the genetic code is a natural outcome of the processes of self-organization that produced it. © 2016 The Author(s).

Exome Sequencing in an Admixed Isolated Population Indicates NFXL1 Variants Confer a Risk for Specific Language Impairment

PubMed Central

Villanueva, Pía; Nudel, Ron; Hoischen, Alexander; Fernández, María Angélica; Simpson, Nuala H.; Gilissen, Christian; Reader, Rose H.; Jara, Lillian; Echeverry, Maria Magdalena; Francks, Clyde; Baird, Gillian; Conti-Ramsden, Gina; O’Hare, Anne; Bolton, Patrick F.; Hennessy, Elizabeth R.; Palomino, Hernán; Carvajal-Carmona, Luis; Veltman, Joris A.; Cazier, Jean-Baptiste; De Barbieri, Zulema

2015-01-01

Children affected by Specific Language Impairment (SLI) fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techniques to investigate an admixed isolated founder population from the Robinson Crusoe Island (Chile), who are affected by a high incidence of SLI, increasing the power to discover contributory genetic factors. We utilize exome sequencing in selected individuals from this population to identify eight coding variants that are of putative significance. We then apply association analyses across the wider population to highlight a single rare coding variant (rs144169475, Minor Allele Frequency of 4.1% in admixed South American populations) in the NFXL1 gene that confers a nonsynonymous change (N150K) and is significantly associated with language impairment in the Robinson Crusoe population (p = 2.04 × 10–4, 8 variants tested). Subsequent sequencing of NFXL1 in 117 UK SLI cases identified four individuals with heterozygous variants predicted to be of functional consequence. We conclude that coding variants within NFXL1 confer an increased risk of SLI within a complex genetic model. PMID:25781923

Phylogenetic relationships within Echinococcus and Taenia tapeworms (Cestoda: Taeniidae): an inference from nuclear protein-coding genes.

PubMed

Knapp, Jenny; Nakao, Minoru; Yanagida, Tetsuya; Okamoto, Munehiro; Saarma, Urmas; Lavikainen, Antti; Ito, Akira

2011-12-01

The family Taeniidae of tapeworms is composed of two genera, Echinococcus and Taenia, which obligately parasitize mammals including humans. Inferring phylogeny via molecular markers is the only way to trace back their evolutionary histories. However, molecular dating approaches are lacking so far. Here we established new markers from nuclear protein-coding genes for RNA polymerase II second largest subunit (rpb2), phosphoenolpyruvate carboxykinase (pepck) and DNA polymerase delta (pold). Bayesian inference and maximum likelihood analyses of the concatenated gene sequences allowed us to reconstruct phylogenetic trees for taeniid parasites. The tree topologies clearly demonstrated that Taenia is paraphyletic and that the clade of Echinococcus oligarthrus and Echinococcusvogeli is sister to all other members of Echinococcus. Both species are endemic in Central and South America, and their definitive hosts originated from carnivores that immigrated from North America after the formation of the Panamanian land bridge about 3 million years ago (Ma). A time-calibrated phylogeny was estimated by a Bayesian relaxed-clock method based on the assumption that the most recent common ancestor of E. oligarthrus and E. vogeli existed during the late Pliocene (3.0 Ma). The results suggest that a clade of Taenia including human-pathogenic species diversified primarily in the late Miocene (11.2 Ma), whereas Echinococcus started to diversify later, in the end of the Miocene (5.8 Ma). Close genetic relationships among the members of Echinococcus imply that the genus is a young group in which speciation and global radiation occurred rapidly. Copyright © 2011 Elsevier Inc. All rights reserved.

DigitSeis: A New Digitization Software and its Application to the Harvard-Adam Dziewoński Observatory Collection

NASA Astrophysics Data System (ADS)

Bogiatzis, P.; Altoé, I. L.; Karamitrou, A.; Ishii, M.; Ishii, H.

2015-12-01

DigitSeis is a new open-source, interactive digitization software written in MATLAB that converts digital, raster images of analog seismograms to readily usable, discretized time series using image processing algorithms. DigitSeis automatically identifies and corrects for various geometrical distortions of seismogram images that are acquired through the original recording, storage, and scanning procedures. With human supervision, the software further identifies and classifies important features such as time marks and notes, corrects time-mark offsets from the main trace, and digitizes the combined trace with an analysis to obtain as accurate timing as possible. Although a large effort has been made to minimize the human input, DigitSeis provides interactive tools for challenging situations such as trace crossings and stains in the paper. The effectiveness of the software is demonstrated with the digitization of seismograms that are over half a century old from the Harvard-Adam Dziewoński observatory that is still in operation as a part of the Global Seismographic Network (station code HRV and network code IU). The spectral analysis of the digitized time series shows no spurious features that may be related to the occurrence of minute and hour marks. They also display signals associated with significant earthquakes, and a comparison of the spectrograms with modern recordings reveals similarities in the background noise.

Decoding the complex genetic causes of heart diseases using systems biology.

PubMed

Djordjevic, Djordje; Deshpande, Vinita; Szczesnik, Tomasz; Yang, Andrian; Humphreys, David T; Giannoulatou, Eleni; Ho, Joshua W K

2015-03-01

The pace of disease gene discovery is still much slower than expected, even with the use of cost-effective DNA sequencing and genotyping technologies. It is increasingly clear that many inherited heart diseases have a more complex polygenic aetiology than previously thought. Understanding the role of gene-gene interactions, epigenetics, and non-coding regulatory regions is becoming increasingly critical in predicting the functional consequences of genetic mutations identified by genome-wide association studies and whole-genome or exome sequencing. A systems biology approach is now being widely employed to systematically discover genes that are involved in heart diseases in humans or relevant animal models through bioinformatics. The overarching premise is that the integration of high-quality causal gene regulatory networks (GRNs), genomics, epigenomics, transcriptomics and other genome-wide data will greatly accelerate the discovery of the complex genetic causes of congenital and complex heart diseases. This review summarises state-of-the-art genomic and bioinformatics techniques that are used in accelerating the pace of disease gene discovery in heart diseases. Accompanying this review, we provide an interactive web-resource for systems biology analysis of mammalian heart development and diseases, CardiacCode ( http://CardiacCode.victorchang.edu.au/ ). CardiacCode features a dataset of over 700 pieces of manually curated genetic or molecular perturbation data, which enables the inference of a cardiac-specific GRN of 280 regulatory relationships between 33 regulator genes and 129 target genes. We believe this growing resource will fill an urgent unmet need to fully realise the true potential of predictive and personalised genomic medicine in tackling human heart disease.

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

Petitpas, Guillaume; Whitesides, Russel

UQHCCI_2 propagates the uncertainties of mass-average quantities (temperature, heat capacity ratio) and the output performances (IMEP, heat release, CA50 and RI) of a HCCI engine test bench using the pressure trace, and intake and exhaust molar fraction and IVC temperature distributions, as inputs (those inputs may be computed using another code UQHCCI_2, or entered independently).

Learning ESL Literacy among Indo-Canadian Women.

ERIC Educational Resources Information Center

Cumming, Alister; Gill, Jaswinder

1991-01-01

Reports findings from an action research project that set up an instructional program for Punjabi-speaking women immigrants and traced their English and literacy development in classroom and home settings. Data indicate that efforts to teach and acquire literacy focused on language code; self-control strategies and schematic representations for…

Nonimaging light concentration using total internal reflection films.

PubMed

Ouellette, G; Waltham, C E; Drees, R M; Poon, A; Schubank, R; Whitehead, L A

1992-05-01

We present a method of fabricating nonimaging light concentrators from total internal reflection film. A prototype has been made and tested and found to operate in agreement with predictions of ray-tracing codes. The performance of the prototype is comparable with that of concentrators made from specular reflecting materials.

Harnessing epigenome modifications for better crops

USDA-ARS?s Scientific Manuscript database

Chemical DNA modifications such as methylation influence translation of the DNA code to specific genetic outcomes. While such modifications can be heritable, others are transient, and their overall contribution to plant genetic diversity remains intriguing but uncertain. The focus of this article is...

A New Inversion Routine to Produce Vertical Electron-Density Profiles from Ionospheric Topside-Sounder Data

NASA Technical Reports Server (NTRS)

Wang, Yongli; Benson, Robert F.

2011-01-01

Two software applications have been produced specifically for the analysis of some million digital topside ionograms produced by a recent analog-to-digital conversion effort of selected analog telemetry tapes from the Alouette-2, ISIS-1 and ISIS-2 satellites. One, TOPIST (TOPside Ionogram Scalar with True-height algorithm) from the University of Massachusetts Lowell, is designed for the automatic identification of the topside-ionogram ionospheric-reflection traces and their inversion into vertical electron-density profiles Ne(h). TOPIST also has the capability of manual intervention. The other application, from the Goddard Space Flight Center based on the FORTRAN code of John E. Jackson from the 1960s, is designed as an IDL-based interactive program for the scaling of selected digital topside-sounder ionograms. The Jackson code has also been modified, with some effort, so as to run on modern computers. This modification was motivated by the need to scale selected ionograms from the millions of Alouette/ISIS topside-sounder ionograms that only exist on 35-mm film. During this modification, it became evident that it would be more efficient to design a new code, based on the capabilities of present-day computers, than to continue to modify the old code. Such a new code has been produced and here we will describe its capabilities and compare Ne(h) profiles produced from it with those produced by the Jackson code. The concept of the new code is to assume an initial Ne(h) and derive a final Ne(h) through an iteration process that makes the resulting apparent-height profile fir the scaled values within a certain error range. The new code can be used on the X-, O-, and Z-mode traces. It does not assume any predefined profile shape between two contiguous points, like the exponential rule used in Jackson s program. Instead, Monotone Piecewise Cubic Interpolation is applied in the global profile to keep the monotone nature of the profile, which also ensures better smoothness in the final profile than in Jackson s program. The new code uses the complete refractive index expression for a cold collisionless plasma and can accommodate the IGRF, T96, and other geomagnetic field models.

Informational structure of genetic sequences and nature of gene splicing

NASA Astrophysics Data System (ADS)

Trifonov, E. N.

1991-10-01

Only about 1/20 of DNA of higher organisms codes for proteins, by means of classical triplet code. The rest of DNA sequences is largely silent, with unclear functions, if any. The triplet code is not the only code (message) carried by the sequences. There are three levels of molecular communication, where the same sequence ``talks'' to various bimolecules, while having, respectively, three different appearances: DNA, RNA and protein. Since the molecular structures and, hence, sequence specific preferences of these are substantially different, the original DNA sequence has to carry simultaneously three types of sequence patterns (codes, messages), thus, being a composite structure in which one had the same letter (nucleotide) is frequently involved in several overlapping codes of different nature. This multiplicity and overlapping of the codes is a unique feature of the Gnomic, language of genetic sequences. The coexisting codes have to be degenerate in various degrees to allow an optimal and concerted performance of all the encoded functions. There is an obvious conflict between the best possible performance of a given function and necessity to compromise the quality of a given sequence pattern in favor of other patterns. It appears that the major role of various changes in the sequences on their ``ontogenetic'' way from DNA to RNA to protein, like RNA editing and splicing, or protein post-translational modifications is to resolve such conflicts. New data are presented strongly indicating that the gene splicing is such a device to resolve the conflict between the code of DNA folding in chromatin and the triplet code for protein synthesis.

Novel base-pairing interactions at the tRNA wobble position crucial for accurate reading of the genetic code

PubMed Central

Rozov, Alexey; Demeshkina, Natalia; Khusainov, Iskander; Westhof, Eric; Yusupov, Marat; Yusupova, Gulnara

2016-01-01

Posttranscriptional modifications at the wobble position of transfer RNAs play a substantial role in deciphering the degenerate genetic code on the ribosome. The number and variety of modifications suggest different mechanisms of action during messenger RNA decoding, of which only a few were described so far. Here, on the basis of several 70S ribosome complex X-ray structures, we demonstrate how Escherichia coli tRNALysUUU with hypermodified 5-methylaminomethyl-2-thiouridine (mnm5s2U) at the wobble position discriminates between cognate codons AAA and AAG, and near-cognate stop codon UAA or isoleucine codon AUA, with which it forms pyrimidine–pyrimidine mismatches. We show that mnm5s2U forms an unusual pair with guanosine at the wobble position that expands general knowledge on the degeneracy of the genetic code and specifies a powerful role of tRNA modifications in translation. Our models consolidate the translational fidelity mechanism proposed previously where the steric complementarity and shape acceptance dominate the decoding mechanism. PMID:26791911

Beyond terrestrial biology: charting the chemical universe of α-amino acid structures.

PubMed

Meringer, Markus; Cleaves, H James; Freeland, Stephen J

2013-11-25

α-Amino acids are fundamental to biochemistry as the monomeric building blocks with which cells construct proteins according to genetic instructions. However, the 20 amino acids of the standard genetic code represent a tiny fraction of the number of α-amino acid chemical structures that could plausibly play such a role, both from the perspective of natural processes by which life emerged and evolved, and from the perspective of human-engineered genetically coded proteins. Until now, efforts to describe the structures comprising this broader set, or even estimate their number, have been hampered by the complex combinatorial properties of organic molecules. Here, we use computer software based on graph theory and constructive combinatorics in order to conduct an efficient and exhaustive search of the chemical structures implied by two careful and precise definitions of the α-amino acids relevant to coded biological proteins. Our results include two virtual libraries of α-amino acid structures corresponding to these different approaches, comprising 121 044 and 3 846 structures, respectively, and suggest a simple approach to exploring much larger, as yet uncomputed, libraries of interest.

Generation of a variety of stable Influenza A reporter viruses by genetic engineering of the NS gene segment

PubMed Central

Reuther, Peter; Göpfert, Kristina; Dudek, Alexandra H.; Heiner, Monika; Herold, Susanne; Schwemmle, Martin

2015-01-01

Influenza A viruses (IAV) pose a constant threat to the human population and therefore a better understanding of their fundamental biology and identification of novel therapeutics is of upmost importance. Various reporter-encoding IAV were generated to achieve these goals, however, one recurring difficulty was the genetic instability especially of larger reporter genes. We employed the viral NS segment coding for the non-structural protein 1 (NS1) and nuclear export protein (NEP) for stable expression of diverse reporter proteins. This was achieved by converting the NS segment into a single open reading frame (ORF) coding for NS1, the respective reporter and NEP. To allow expression of individual proteins, the reporter genes were flanked by two porcine Teschovirus-1 2A peptide (PTV-1 2A)-coding sequences. The resulting viruses encoding luciferases, fluorescent proteins or a Cre recombinase are characterized by a high genetic stability in vitro and in mice and can be readily employed for antiviral compound screenings, visualization of infected cells or cells that survived acute infection. PMID:26068081

Long noncoding RNAs and tumorigenesis: genetic associations, molecular mechanisms, and therapeutic strategies.

PubMed

Zhang, Fan; Zhang, Liang; Zhang, Caiguo

2016-01-01

The human genome contains a large number of nonprotein-coding sequences. Recently, new discoveries in the functions of nonprotein-coding sequences have demonstrated that the "Dark Genome" significantly contributes to human diseases, especially with regard to cancer. Of particular interest in this review are long noncoding RNAs (lncRNAs), which comprise a class of nonprotein-coding transcripts that are longer than 200 nucleotides. Accumulating evidence indicates that a large number of lncRNAs exhibit genetic associations with tumorigenesis, tumor progression, and metastasis. Our current understanding of the molecular bases of these lncRNAs that are associated with cancer indicate that they play critical roles in gene transcription, translation, and chromatin modification. Therapeutic strategies based on the targeting of lncRNAs to disrupt their expression or their functions are being developed. In this review, we briefly summarize and discuss the genetic associations and the aberrant expression of lncRNAs in cancer, with a particular focus on studies that have revealed the molecular mechanisms of lncRNAs in tumorigenesis. In addition, we also discuss different therapeutic strategies that involve the targeting of lncRNAs.

Novel base-pairing interactions at the tRNA wobble position crucial for accurate reading of the genetic code.

PubMed

Rozov, Alexey; Demeshkina, Natalia; Khusainov, Iskander; Westhof, Eric; Yusupov, Marat; Yusupova, Gulnara

2016-01-21

Posttranscriptional modifications at the wobble position of transfer RNAs play a substantial role in deciphering the degenerate genetic code on the ribosome. The number and variety of modifications suggest different mechanisms of action during messenger RNA decoding, of which only a few were described so far. Here, on the basis of several 70S ribosome complex X-ray structures, we demonstrate how Escherichia coli tRNA(Lys)(UUU) with hypermodified 5-methylaminomethyl-2-thiouridine (mnm(5)s(2)U) at the wobble position discriminates between cognate codons AAA and AAG, and near-cognate stop codon UAA or isoleucine codon AUA, with which it forms pyrimidine-pyrimidine mismatches. We show that mnm(5)s(2)U forms an unusual pair with guanosine at the wobble position that expands general knowledge on the degeneracy of the genetic code and specifies a powerful role of tRNA modifications in translation. Our models consolidate the translational fidelity mechanism proposed previously where the steric complementarity and shape acceptance dominate the decoding mechanism.

Novel base-pairing interactions at the tRNA wobble position crucial for accurate reading of the genetic code

NASA Astrophysics Data System (ADS)

Rozov, Alexey; Demeshkina, Natalia; Khusainov, Iskander; Westhof, Eric; Yusupov, Marat; Yusupova, Gulnara

2016-01-01

Posttranscriptional modifications at the wobble position of transfer RNAs play a substantial role in deciphering the degenerate genetic code on the ribosome. The number and variety of modifications suggest different mechanisms of action during messenger RNA decoding, of which only a few were described so far. Here, on the basis of several 70S ribosome complex X-ray structures, we demonstrate how Escherichia coli tRNALysUUU with hypermodified 5-methylaminomethyl-2-thiouridine (mnm5s2U) at the wobble position discriminates between cognate codons AAA and AAG, and near-cognate stop codon UAA or isoleucine codon AUA, with which it forms pyrimidine-pyrimidine mismatches. We show that mnm5s2U forms an unusual pair with guanosine at the wobble position that expands general knowledge on the degeneracy of the genetic code and specifies a powerful role of tRNA modifications in translation. Our models consolidate the translational fidelity mechanism proposed previously where the steric complementarity and shape acceptance dominate the decoding mechanism.

Conservation genetics and geographic patterns of genetic variation of the endangered officinal herb Fritillaria pallidiflora

Treesearch

Zhihao Su; Borong Pan; Stewart C. Sanderson; Xiaolong Jiang; Mingli Zhang

2015-01-01

Fritillaria pallidiflora is an endangered officinal herb distributed in the Tianshan Mountains of northwestern China. We examined its phylogeography to study evolutionary processes and suggest implications for conservation. Six haplotypes were detected based on three chloroplast non-coding spacers (psbA-trnH, rps16, and trnS-trnG); genetic variation mainly occurred...

The Future of Genetics in Psychology and Psychiatry: Microarrays, Genome-Wide Association, and Non-Coding RNA

ERIC Educational Resources Information Center

Plomin, Robert; Davis, Oliver S. P.

2009-01-01

Background: Much of what we thought we knew about genetics needs to be modified in light of recent discoveries. What are the implications of these advances for identifying genes responsible for the high heritability of many behavioural disorders and dimensions in childhood? Methods: Although quantitative genetics such as twin studies will continue…

Trace elements in Antarctic meteorites: Weathering and genetic information

NASA Technical Reports Server (NTRS)

Lipschutz, M. E.

1986-01-01

Antarctic meteorite discoveries have created great scientific interest due to the large number of specimens recovered (approximately 7000) and because included are representatives of hitherto rare or unknown types. Antarctic meteorites are abundant because they have fallen over long periods and were preserved, transported, and concentrated by the ice sheets. The weathering effects on the Antarctic meteorites are described. Weathering effects of trace element contents of H5 chondrites were studied in detail. The results are examined. The properties of Antarctic finds and non-Antarctic falls are discussed.

MHC class I diversity in chimpanzees and bonobos.

PubMed

Maibach, Vincent; Hans, Jörg B; Hvilsom, Christina; Marques-Bonet, Tomas; Vigilant, Linda

2017-10-01

Major histocompatibility complex (MHC) class I genes are critically involved in the defense against intracellular pathogens. MHC diversity comparisons among samples of closely related taxa may reveal traces of past or ongoing selective processes. The bonobo and chimpanzee are the closest living evolutionary relatives of humans and last shared a common ancestor some 1 mya. However, little is known concerning MHC class I diversity in bonobos or in central chimpanzees, the most numerous and genetically diverse chimpanzee subspecies. Here, we used a long-read sequencing technology (PacBio) to sequence the classical MHC class I genes A, B, C, and A-like in 20 and 30 wild-born bonobos and chimpanzees, respectively, with a main focus on central chimpanzees to assess and compare diversity in those two species. We describe in total 21 and 42 novel coding region sequences for the two species, respectively. In addition, we found evidence for a reduced MHC class I diversity in bonobos as compared to central chimpanzees as well as to western chimpanzees and humans. The reduced bonobo MHC class I diversity may be the result of a selective process in their evolutionary past since their split from chimpanzees.

Exome chip meta-analysis identifies novel loci and East Asian-specific coding variants that contribute to lipid levels and coronary artery disease.

PubMed

Lu, Xiangfeng; Peloso, Gina M; Liu, Dajiang J; Wu, Ying; Zhang, He; Zhou, Wei; Li, Jun; Tang, Clara Sze-Man; Dorajoo, Rajkumar; Li, Huaixing; Long, Jirong; Guo, Xiuqing; Xu, Ming; Spracklen, Cassandra N; Chen, Yang; Liu, Xuezhen; Zhang, Yan; Khor, Chiea Chuen; Liu, Jianjun; Sun, Liang; Wang, Laiyuan; Gao, Yu-Tang; Hu, Yao; Yu, Kuai; Wang, Yiqin; Cheung, Chloe Yu Yan; Wang, Feijie; Huang, Jianfeng; Fan, Qiao; Cai, Qiuyin; Chen, Shufeng; Shi, Jinxiu; Yang, Xueli; Zhao, Wanting; Sheu, Wayne H-H; Cherny, Stacey Shawn; He, Meian; Feranil, Alan B; Adair, Linda S; Gordon-Larsen, Penny; Du, Shufa; Varma, Rohit; Chen, Yii-Der Ida; Shu, Xiao-Ou; Lam, Karen Siu Ling; Wong, Tien Yin; Ganesh, Santhi K; Mo, Zengnan; Hveem, Kristian; Fritsche, Lars G; Nielsen, Jonas Bille; Tse, Hung-Fat; Huo, Yong; Cheng, Ching-Yu; Chen, Y Eugene; Zheng, Wei; Tai, E Shyong; Gao, Wei; Lin, Xu; Huang, Wei; Abecasis, Goncalo; Kathiresan, Sekar; Mohlke, Karen L; Wu, Tangchun; Sham, Pak Chung; Gu, Dongfeng; Willer, Cristen J

2017-12-01

Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After a meta-analysis including >300,000 European samples, we identified an additional nine novel loci. Sixteen genes were identified by protein-altering variants in both East Asians and Europeans, and thus are likely to be functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci.

Exome chip meta-analysis identifies novel loci and East Asian-specific coding variants contributing to lipid levels and coronary artery disease

PubMed Central

Lu, Xiangfeng; Peloso, Gina M; Liu, Dajiang J.; Wu, Ying; Zhang, He; Zhou, Wei; Li, Jun; Tang, Clara Sze-man; Dorajoo, Rajkumar; Li, Huaixing; Long, Jirong; Guo, Xiuqing; Xu, Ming; Spracklen, Cassandra N.; Chen, Yang; Liu, Xuezhen; Zhang, Yan; Khor, Chiea Chuen; Liu, Jianjun; Sun, Liang; Wang, Laiyuan; Gao, Yu-Tang; Hu, Yao; Yu, Kuai; Wang, Yiqin; Cheung, Chloe Yu Yan; Wang, Feijie; Huang, Jianfeng; Fan, Qiao; Cai, Qiuyin; Chen, Shufeng; Shi, Jinxiu; Yang, Xueli; Zhao, Wanting; Sheu, Wayne H.-H.; Cherny, Stacey Shawn; He, Meian; Feranil, Alan B.; Adair, Linda S.; Gordon-Larsen, Penny; Du, Shufa; Varma, Rohit; da Chen, Yii-Der I; Shu, XiaoOu; Lam, Karen Siu Ling; Wong, Tien Yin; Ganesh, Santhi K.; Mo, Zengnan; Hveem, Kristian; Fritsche, Lars; Nielsen, Jonas Bille; Tse, Hung-fat; Huo, Yong; Cheng, Ching-Yu; Chen, Y. Eugene; Zheng, Wei; Tai, E Shyong; Gao, Wei; Lin, Xu; Huang, Wei; Abecasis, Goncalo; Consortium, GLGC; Kathiresan, Sekar; Mohlke, Karen L.; Wu, Tangchun; Sham, Pak Chung; Gu, Dongfeng; Willer, Cristen J

2017-01-01

Most genome-wide association studies have been conducted in European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we examined protein-coding genetic variants in 47,532 East Asian individuals using an exome array. We identified 255 variants at 41 loci reaching chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After meta-analysis with > 300,000 European samples, we identified an additional 9 novel loci. The same 16 genes were identified by the protein-altering variants in both East Asians and Europeans, likely pointing to the functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population-specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci. PMID:29083407

Shannon Entropy of the Canonical Genetic Code

NASA Astrophysics Data System (ADS)

Nemzer, Louis

The probability that a non-synonymous point mutation in DNA will adversely affect the functionality of the resultant protein is greatly reduced if the substitution is conservative. In that case, the amino acid coded by the mutated codon has similar physico-chemical properties to the original. Many simplified alphabets, which group the 20 common amino acids into families, have been proposed. To evaluate these schema objectively, we introduce a novel, quantitative method based on the inherent redundancy in the canonical genetic code. By calculating the Shannon information entropy carried by 1- or 2-bit messages, groupings that best leverage the robustness of the code are identified. The relative importance of properties related to protein folding - like hydropathy and size - and function, including side-chain acidity, can also be estimated. In addition, this approach allows us to quantify the average information value of nucleotide codon positions, and explore the physiological basis for distinguishing between transition and transversion mutations. Supported by NSU PFRDG Grant #335347.

Application of computational fluid dynamics and laminar flow technology for improved performance and sonic boom reduction

NASA Technical Reports Server (NTRS)

Bobbitt, Percy J.

1992-01-01

A discussion is given of the many factors that affect sonic booms with particular emphasis on the application and development of improved computational fluid dynamics (CFD) codes. The benefits that accrue from interference (induced) lift, distributing lift using canard configurations, the use of wings with dihedral or anhedral and hybrid laminar flow control for drag reduction are detailed. The application of the most advanced codes to a wider variety of configurations along with improved ray-tracing codes to arrive at more accurate and, hopefully, lower sonic booms is advocated. Finally, it is speculated that when all of the latest technology is applied to the design of a supersonic transport it will be found environmentally acceptable.

The origins of informed consent: the International Scientific Commission on Medical War Crimes, and the Nuremburg code.

PubMed

Weindling, P

2001-01-01

The Nuremberg Code has generally been seen as arising from the Nuremberg Medical Trial. This paper examines developments prior to the Trial, involving the physiologist Andrew Conway Ivy and an inter-Allied Scientific Commission on Medical War Crimes. The paper traces the formulation of the concept of a medical war crime by the physiologist John West Thompson, as part of the background to Ivy's code on human experiments of 1 August 1946. It evaluates subsequent responses by the American Medical Association, and by other war crimes experts, notably Leo Alexander, who developed Ivy's conceptual framework. Ivy's interaction with the judges at Nuremberg alerted them to the importance of formulating ethical guidelines for clinical research.

Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy.

PubMed

Lee, Yi; El Andaloussi, Samir; Wood, Matthew J A

2012-10-15

Exosomes and microvesicles are extracellular nanovesicles released by most but not all cells. They are specifically equipped to mediate intercellular communication via the transfer of genetic information, including the transfer of both coding and non-coding RNAs, to recipient cells. As a result, both exosomes and microvesicles play a fundamental biological role in the regulation of normal physiological as well as aberrant pathological processes, via altered gene regulatory networks and/or via epigenetic programming. For example, microvesicle-mediated genetic transfer can regulate the maintenance of stem cell plasticity and induce beneficial cell phenotype modulation. Alternatively, such vesicles play a role in tumor pathogenesis and the spread of neurodegenerative diseases via the transfer of specific microRNAs and pathogenic proteins. Given this natural property for genetic information transfer, the possibility of exploiting these vesicles for therapeutic purposes is now being investigated. Stem cell-derived microvesicles appear to be naturally equipped to mediate tissue regeneration under certain conditions, while recent evidence suggests that exosomes might be harnessed for the targeted delivery of human genetic therapies via the introduction of exogenous genetic cargoes such as siRNA. Thus, extracellular vesicles are emerging as potent genetic information transfer agents underpinning a range of biological processes and with therapeutic potential.

Improved genetic algorithm for the protein folding problem by use of a Cartesian combination operator.

PubMed Central

Rabow, A. A.; Scheraga, H. A.

1996-01-01

We have devised a Cartesian combination operator and coding scheme for improving the performance of genetic algorithms applied to the protein folding problem. The genetic coding consists of the C alpha Cartesian coordinates of the protein chain. The recombination of the genes of the parents is accomplished by: (1) a rigid superposition of one parent chain on the other, to make the relation of Cartesian coordinates meaningful, then, (2) the chains of the children are formed through a linear combination of the coordinates of their parents. The children produced with this Cartesian combination operator scheme have similar topology and retain the long-range contacts of their parents. The new scheme is significantly more efficient than the standard genetic algorithm methods for locating low-energy conformations of proteins. The considerable superiority of genetic algorithms over Monte Carlo optimization methods is also demonstrated. We have also devised a new dynamic programming lattice fitting procedure for use with the Cartesian combination operator method. The procedure finds excellent fits of real-space chains to the lattice while satisfying bond-length, bond-angle, and overlap constraints. PMID:8880904

A simplified fractional order impedance model and parameter identification method for lithium-ion batteries

PubMed Central

Yang, Qingxia; Xu, Jun; Cao, Binggang; Li, Xiuqing

2017-01-01

Identification of internal parameters of lithium-ion batteries is a useful tool to evaluate battery performance, and requires an effective model and algorithm. Based on the least square genetic algorithm, a simplified fractional order impedance model for lithium-ion batteries and the corresponding parameter identification method were developed. The simplified model was derived from the analysis of the electrochemical impedance spectroscopy data and the transient response of lithium-ion batteries with different states of charge. In order to identify the parameters of the model, an equivalent tracking system was established, and the method of least square genetic algorithm was applied using the time-domain test data. Experiments and computer simulations were carried out to verify the effectiveness and accuracy of the proposed model and parameter identification method. Compared with a second-order resistance-capacitance (2-RC) model and recursive least squares method, small tracing voltage fluctuations were observed. The maximum battery voltage tracing error for the proposed model and parameter identification method is within 0.5%; this demonstrates the good performance of the model and the efficiency of the least square genetic algorithm to estimate the internal parameters of lithium-ion batteries. PMID:28212405

Mammalian molybdo-flavoenzymes, an expanding family of proteins: structure, genetics, regulation, function and pathophysiology.

PubMed Central

Garattini, Enrico; Mendel, Ralf; Romão, Maria João; Wright, Richard; Terao, Mineko

2003-01-01

The molybdo-flavoenzymes are structurally related proteins that require a molybdopterin cofactor and FAD for their catalytic activity. In mammals, four enzymes are known: xanthine oxidoreductase, aldehyde oxidase and two recently described mouse proteins known as aldehyde oxidase homologue 1 and aldehyde oxidase homologue 2. The present review article summarizes current knowledge on the structure, enzymology, genetics, regulation and pathophysiology of mammalian molybdo-flavoenzymes. Molybdo-flavoenzymes are structurally complex oxidoreductases with an equally complex mechanism of catalysis. Our knowledge has greatly increased due to the recent crystallization of two xanthine oxidoreductases and the determination of the amino acid sequences of many members of the family. The evolution of molybdo-flavoenzymes can now be traced, given the availability of the structures of the corresponding genes in many organisms. The genes coding for molybdo-flavoenzymes are expressed in a cell-specific fashion and are controlled by endogenous and exogenous stimuli. The recent cloning of the genes involved in the biosynthesis of the molybdenum cofactor has increased our knowledge on the assembly of the apo-forms of molybdo-flavoproteins into the corresponding holo-forms. Xanthine oxidoreductase is the key enzyme in the catabolism of purines, although recent data suggest that the physiological function of this enzyme is more complex than previously assumed. The enzyme has been implicated in such diverse pathological situations as organ ischaemia, inflammation and infection. At present, very little is known about the pathophysiological relevance of aldehyde oxidase, aldehyde oxidase homologue 1 and aldehyde oxidase homologue 2, which do not as yet have an accepted endogenous substrate. PMID:12578558

The importance of immune gene variability (MHC) in evolutionary ecology and conservation

PubMed Central

Sommer, Simone

2005-01-01

Genetic studies have typically inferred the effects of human impact by documenting patterns of genetic differentiation and levels of genetic diversity among potentially isolated populations using selective neutral markers such as mitochondrial control region sequences, microsatellites or single nucleotide polymorphism (SNPs). However, evolutionary relevant and adaptive processes within and between populations can only be reflected by coding genes. In vertebrates, growing evidence suggests that genetic diversity is particularly important at the level of the major histocompatibility complex (MHC). MHC variants influence many important biological traits, including immune recognition, susceptibility to infectious and autoimmune diseases, individual odours, mating preferences, kin recognition, cooperation and pregnancy outcome. These diverse functions and characteristics place genes of the MHC among the best candidates for studies of mechanisms and significance of molecular adaptation in vertebrates. MHC variability is believed to be maintained by pathogen-driven selection, mediated either through heterozygote advantage or frequency-dependent selection. Up to now, most of our knowledge has derived from studies in humans or from model organisms under experimental, laboratory conditions. Empirical support for selective mechanisms in free-ranging animal populations in their natural environment is rare. In this review, I first introduce general information about the structure and function of MHC genes, as well as current hypotheses and concepts concerning the role of selection in the maintenance of MHC polymorphism. The evolutionary forces acting on the genetic diversity in coding and non-coding markers are compared. Then, I summarise empirical support for the functional importance of MHC variability in parasite resistance with emphasis on the evidence derived from free-ranging animal populations investigated in their natural habitat. Finally, I discuss the importance of adaptive genetic variability with respect to human impact and conservation, and implications for future studies. PMID:16242022

JavaGenes and Condor: Cycle-Scavenging Genetic Algorithms

NASA Technical Reports Server (NTRS)

Globus, Al; Langhirt, Eric; Livny, Miron; Ramamurthy, Ravishankar; Soloman, Marvin; Traugott, Steve

2000-01-01

A genetic algorithm code, JavaGenes, was written in Java and used to evolve pharmaceutical drug molecules and digital circuits. JavaGenes was run under the Condor cycle-scavenging batch system managing 100-170 desktop SGI workstations. Genetic algorithms mimic biological evolution by evolving solutions to problems using crossover and mutation. While most genetic algorithms evolve strings or trees, JavaGenes evolves graphs representing (currently) molecules and circuits. Java was chosen as the implementation language because the genetic algorithm requires random splitting and recombining of graphs, a complex data structure manipulation with ample opportunities for memory leaks, loose pointers, out-of-bound indices, and other hard to find bugs. Java garbage-collection memory management, lack of pointer arithmetic, and array-bounds index checking prevents these bugs from occurring, substantially reducing development time. While a run-time performance penalty must be paid, the only unacceptable performance we encountered was using standard Java serialization to checkpoint and restart the code. This was fixed by a two-day implementation of custom checkpointing. JavaGenes is minimally integrated with Condor; in other words, JavaGenes must do its own checkpointing and I/O redirection. A prototype Java-aware version of Condor was developed using standard Java serialization for checkpointing. For the prototype to be useful, standard Java serialization must be significantly optimized. JavaGenes is approximately 8700 lines of code and a few thousand JavaGenes jobs have been run. Most jobs ran for a few days. Results include proof that genetic algorithms can evolve directed and undirected graphs, development of a novel crossover operator for graphs, a paper in the journal Nanotechnology, and another paper in preparation.

Characterization and phylogenetic analysis of the swine leukocyte antigen 3 gene from Korean native pigs.

PubMed

Chung, H Y; Choi, Y C; Park, H N

2015-05-18

We investigated the phylogenetic relationships between pig breeds, compared the genetic similarity between humans and pigs, and provided basic genetic information on Korean native pigs (KNPs), using genetic variants of the swine leukocyte antigen 3 (SLA-3) gene. Primers were based on sequences from GenBank (accession Nos. AF464010 and AF464009). Polymerase chain reaction analysis amplified approximately 1727 bp of segments, which contained 1086 bp of coding regions and 641 bp of the 3'- and 5'-untranslated regions. Bacterial artificial chromosome clones of miniature pigs were used for sequencing the SLA-3 genomic region, which was 3114 bp in total length, including the coding (1086 bp) and non-coding (2028 bp) regions. Sequence analysis detected 53 single nucleotide polymorphisms (SNPs), based on a minor allele frequency greater than 0.01, which is low compared with other pig breeds, and the results suggest that there is low genetic variability in KNPs. Comparative analysis revealed that humans possess approximately three times more genetic variation than do pigs. Approximately 71% of SNPs in exons 2 and 3 were detected in KNPs, and exon 5 in humans is a highly polymorphic region. Newly identified sequences of SLA-3 using KNPs were submitted to GenBank (accession No. DQ992512-18). Cluster analysis revealed that KNPs were grouped according to three major alleles: SLA-3*0502 (DQ992518), SLA-3*0302 (DQ992513 and DQ992516), and SLA-3*0303 (DQ992512, DQ992514, DQ992515, and DQ992517). Alignments revealed that humans have a relatively close genetic relationship with pigs and chimpanzees. The information provided by this study may be useful in KNP management.

Development of battering ram vibrator system

NASA Astrophysics Data System (ADS)

Sun, F.; Chen, Z.; Lin, J.; Tong, X.

2012-12-01

This paper researched the battering ram vibrator system, by electric machinery we can control oil system of battering ram, we realized exact control of battering ram, after analyzed pseudorandom coding, code "0" and "1" correspond to rest and shake of battering ram, then we can get pseudorandom coding which is the same with battering ram vibrator. After testing , by the reference trace and single shot record, when we using pseudorandom coding mode, the ratio of seismic wavelet to correlation interfere is about 68 dB, while the general mode , the ratio of seismic wavelet to correlation interfere only is 27.9dB, by battering ram vibrator system, we can debase the correlation interfere which come from the single shaking frequency of battering ram, this system advanced the signal-to-noise ratio of seismic data, which can give direction of the application of battering ram vibrator in metal mine exploration and high resolving seismic exploration.

Simulations of Laboratory Astrophysics Experiments using the CRASH code

NASA Astrophysics Data System (ADS)

Trantham, Matthew; Kuranz, Carolyn; Manuel, Mario; Keiter, Paul; Drake, R. P.

2014-10-01

Computer simulations can assist in the design and analysis of laboratory astrophysics experiments. The Center for Radiative Shock Hydrodynamics (CRASH) at the University of Michigan developed a code that has been used to design and analyze high-energy-density experiments on OMEGA, NIF, and other large laser facilities. This Eulerian code uses block-adaptive mesh refinement (AMR) with implicit multigroup radiation transport, electron heat conduction and laser ray tracing. This poster/talk will demonstrate some of the experiments the CRASH code has helped design or analyze including: Kelvin-Helmholtz, Rayleigh-Taylor, imploding bubbles, and interacting jet experiments. This work is funded by the Predictive Sciences Academic Alliances Program in NNSA-ASC via Grant DEFC52-08NA28616, by the NNSA-DS and SC-OFES Joint Program in High-Energy-Density Laboratory Plasmas, Grant Number DE-NA0001840, and by the National Laser User Facility Program, Grant Number DE-NA0000850.

METHES: A Monte Carlo collision code for the simulation of electron transport in low temperature plasmas

NASA Astrophysics Data System (ADS)

Rabie, M.; Franck, C. M.

2016-06-01

We present a freely available MATLAB code for the simulation of electron transport in arbitrary gas mixtures in the presence of uniform electric fields. For steady-state electron transport, the program provides the transport coefficients, reaction rates and the electron energy distribution function. The program uses established Monte Carlo techniques and is compatible with the electron scattering cross section files from the open-access Plasma Data Exchange Project LXCat. The code is written in object-oriented design, allowing the tracing and visualization of the spatiotemporal evolution of electron swarms and the temporal development of the mean energy and the electron number due to attachment and/or ionization processes. We benchmark our code with well-known model gases as well as the real gases argon, N2, O2, CF4, SF6 and mixtures of N2 and O2.

Utilization of genetic tests: analysis of gene-specific billing in Medicare claims data.

PubMed

Lynch, Julie A; Berse, Brygida; Dotson, W David; Khoury, Muin J; Coomer, Nicole; Kautter, John

2017-08-01

We examined the utilization of precision medicine tests among Medicare beneficiaries through analysis of gene-specific tier 1 and 2 billing codes developed by the American Medical Association in 2012. We conducted a retrospective cross-sectional study. The primary source of data was 2013 Medicare 100% fee-for-service claims. We identified claims billed for each laboratory test, the number of patients tested, expenditures, and the diagnostic codes indicated for testing. We analyzed variations in testing by patient demographics and region of the country. Pharmacogenetic tests were billed most frequently, accounting for 48% of the expenditures for new codes. The most common indications for testing were breast cancer, long-term use of medications, and disorders of lipid metabolism. There was underutilization of guideline-recommended tumor mutation tests (e.g., epidermal growth factor receptor) and substantial overutilization of a test discouraged by guidelines (methylenetetrahydrofolate reductase). Methodology-based tier 2 codes represented 15% of all claims billed with the new codes. The highest rate of testing per beneficiary was in Mississippi and the lowest rate was in Alaska. Gene-specific billing codes significantly improved our ability to conduct population-level research of precision medicine. Analysis of these data in conjunction with clinical records should be conducted to validate findings.Genet Med advance online publication 26 January 2017.

P1198: software for tracing decision behavior in lending to small businesses.

PubMed

Andersson, P

2001-05-01

This paper describes a process-tracing software program specially designed to capture decision behavior in lending to small businesses. The source code was written in Lotus Notes. The software runs in a Web browser and consists of two interacting systems: a database and a user interface. The database includes three realistic loan applications. The user interface consists of different but interacting screens that enable the participant to operate the software. Log files register the decision behavior of the participant. An empirical example is presented in order to show the software's potential in providing insights into judgment and decision making. The implications of the software are discussed.

MicroRNAs in genetic disease: rethinking the dosage.

PubMed

Henrion-Caude, Alexandra; Girard, Muriel; Amiel, Jeanne

2012-08-01

To date, the general assumption was that most mutations interested protein-coding genes only. Thus, only few illustrations have mentioned here that mutations may occur in non-protein coding genes such as microRNAs (miRNAs). We thus report progress in delineating their contribution as phenotypic modulators, genetic switches and fine-tuners of gene expression. We reasoned that browsing their contribution to genetic disease may provide a framework for understanding the proper requirements to devise miRNA-based therapy strategies, in particular the relief of an appropriate dosage. Gain and loss of function of miRNA enforce the need to respectively antagonize or supply the miRNAs. We further categorized human disease according to the different ways in which the miRNA was altered arising either de novo, or inherited whether as a mendelian or as an epistatic trait, uncovering its role in epigenetics. We discuss how improving our knowledge on the contribution of miRNAs to genetic disease may be beneficial to devise appropriate gene therapy strategies.

Hypothalamic transcriptomes of 99 mouse strains reveal trans eQTL hotspots, splicing QTLs and novel non-coding genes

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

Hasin-Brumshtein, Yehudit; Khan, Arshad H.; Hormozdiari, Farhad

2016-09-13

Previous studies had shown that the integration of genome wide expression profiles, in metabolic tissues, with genetic and phenotypic variance, provided valuable insight into the underlying molecular mechanisms. We used RNA-Seq to characterize hypothalamic transcriptome in 99 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP), a reference resource population for cardiovascular and metabolic traits. We report numerous novel transcripts supported by proteomic analyses, as well as novel non coding RNAs. High resolution genetic mapping of transcript levels in HMDP, reveals bothlocalandtransexpression Quantitative Trait Loci (eQTLs) demonstrating 2transeQTL 'hotspots' associated with expression of hundreds of genes. We alsomore » report thousands of alternative splicing events regulated by genetic variants. Finally, comparison with about 150 metabolic and cardiovascular traits revealed many highly significant associations. Our data provide a rich resource for understanding the many physiologic functions mediated by the hypothalamus and their genetic regulation.« less

Trace samples of human blood in mosquitoes as a forensic investigation tool.

PubMed

Rabêlo, K C N; Albuquerque, C M R; Tavares, V B; Santos, S M; Souza, C A; Oliveira, T C; Oliveira, N C L; Crovella, S

2015-11-23

Investigations of any type of crime invariably starts at the crime scene by collecting evidence. Thus, the purpose of this research was to collect and analyze an entomological trace from an environment that is similar to those of indoor crime scenes. Hematophagous mosquitoes were collected from two residential units; saliva of volunteers that were residents in the units was also collected for genetic analysis as reference samples. We examined the allele frequencies of 15 short tandem repeat loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818, and FGA) and amelogenin. A total of 26 female hematophagous mosquitoes were identified as Aedes aegypti, Aedes albopictus, and Culex quinquefasciatus; we were able to obtain 11 forensically valid genetic profiles, with a minimum of 0.028203 ng/μL of human DNA. Thus, the results of this study showed that it was possible to correlate human genetic information from mosquitoes with the volunteer reference samples, which validates the use of this information as forensic evidence. Furthermore, we observed mixed genetic profiles from one mosquito. Therefore, it is clearly important to collect these insects indoors where crimes were committed, because it may be possible to find intact genetic profiles of suspects in the blood found in the digestive tract of hematophagous mosquitoes for later comparison to identify an offender and/or exclude suspects.

The conservation of forest genetic resources: case histories from Canada, Mexico, and the United States

Treesearch

F. Thomas Ledig; J. Jesús Vargas-Hernández; Kurt H. Johnsen

1998-01-01

The genetic codes of living organisms are natural resources no less than soil, air, and water. Genetic resources-from nucleotide sequences in DNA to selected genotypes, populations, and species-are the raw material in forestry: for breeders, for the forest manager who produces an economic crop, for society that reaps the environmental benefits provided by forests, and...

DNA typing of birch: Development of a forensic STR system for Betula pendula and Betula pubescens.

PubMed

Wesselink, Monique; Dragutinović, Aleksandar; Noordhoek, Jeroen W; Bergwerff, Leonie; Kuiper, Irene

2018-04-07

Although botanical trace evidence is often encountered in case investigations, the utilization of such traces in forensic investigations is still limited. Development of a forensic STR system for the two species of Betula (birch) indigenous to and abundant in North West Europe is a step in enhancing the applicability of traces from these species. We describe six microsatellite markers developed for birch species in detail, including repeat structure, and we propose a nomenclature for the encountered alleles. To assess the population characteristics, the genetic composition of wild, planted and intermediate populations of Betula pendula (a diploid species) and Betula pubescens (a tetraploid species) were investigated. The genetic differences between these two species were larger than the differences between populations of one species, even when both species co-occurred at one location. Therefore allele frequencies were estimated for both species separately. General, conservative random match probabilities were estimated for wild trees based on these allele frequencies (5∙10 -6 for the diploid B. pendula and 1∙10 -13 for the tetraploid B. pubescens), illustrating the potential relevance if trace evidence secured from a suspect is found to match a birch tree growing on or near a crime scene. Apart from wild trees, planted Betula trees also occur that may not originate from seeds, but may have been propagated through cloning. Based on the studied Betula trees, the random match probability of a potentially planted profile might be as high as 1.4∙10 -2 . Copyright © 2018 Elsevier B.V. All rights reserved.

Thermal radiation characteristics of nonisothermal cylindrical enclosures using a numerical ray tracing technique

NASA Technical Reports Server (NTRS)

Baumeister, Joseph F.

1990-01-01

Analysis of energy emitted from simple or complex cavity designs can lead to intricate solutions due to nonuniform radiosity and irradiation within a cavity. A numerical ray tracing technique was applied to simulate radiation propagating within and from various cavity designs. To obtain the energy balance relationships between isothermal and nonisothermal cavity surfaces and space, the computer code NEVADA was utilized for its statistical technique applied to numerical ray tracing. The analysis method was validated by comparing results with known theoretical and limiting solutions, and the electrical resistance network method. In general, for nonisothermal cavities the performance (apparent emissivity) is a function of cylinder length-to-diameter ratio, surface emissivity, and cylinder surface temperatures. The extent of nonisothermal conditions in a cylindrical cavity significantly affects the overall cavity performance. Results are presented over a wide range of parametric variables for use as a possible design reference.

Asymptotic Learning of Alphanumeric Coding in Autobiographical Memory

ERIC Educational Resources Information Center

Martin, Maryanne; Jones, Gregory V.

2007-01-01

Studies of autobiographical memory have shown that observed levels of incidental learning are often relatively low. Do low levels of retention result simply from a low learning rate, or is learning also asymptotic? To address this question, it is necessary to trace performance over a large number of learning opportunities, and this was carried out…

FURTHER STUDIES ON THE γG-HEAVY CHAIN GENE COMPLEXES, WITH PARTICULAR REFERENCE TO THE GENETIC MARKERS Gm(g) AND Gm(n)

PubMed Central

Natvig, J. B.; Kunkel, H. G.; Yount, W. J.; Nielsen, J. C.

1968-01-01

The recently described Gm (g) and Gm (n) genetic markers of the γG3- and γG2-subgroups of γ-globulin were characterized in detail primarily through studies of myeloma proteins, their polypeptide chains and fragments. Antisera derived from rabbits, non-human primates and rheumatoid arthritis patients gave identical results. This contrasted with the Gm (b) system where the rabbit antisera react with a different genetic determinant (b0) than the sera from rheumatoid arthritis patients (b). The Gm (g) and Gm (n) antigens were detected both by precipitin analysis and by hemagglutination inhibition. The Gm (g) antigen was not associated with any of the other genetic antigens of the γG3-proteins which all belonged in the Gm (b) class. The genes for the latter were always allelic to the gene coding for Gm (g), with that for Gm (b0) constantly present when that for Gm (g) was absent. The Gm (g) and Gm (n) markers were of particular value in tracing the various gene complexes made up of the closely linked subgroup genes. Further support was gained for the concept that the different gene complexes of various population groups arose primarily through crossing-over. The Gm g and Gm b genes for the γG3-subgroup were extremely closely linked to those for the γG1-subgroup. However the Gm (n) marker indicated that the γG2-subgroup genes were probably further separated on the chromosome. Additional evidence was obtained for the γG2-γG3-γG1-order of the subgroup cistrons. Among the wide range of gene complexes a new type (γG2,—,γ/G1) was described. This complex appeared to have a deletion of the γG3-cistron. Lower levels of γG3-globulin were found in the sera of the individuals with this gene in the heterozygous state. The possibility that this unusual complex arose through an unequal nonhomologous crossing-over is discussed. PMID:19867305

Using AORSA to simulate helicon waves in DIII-D

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

Lau, C., E-mail: lauch@ornl.gov; Blazevski, D.; Green, D. L.

2015-12-10

Recent efforts have shown that helicon waves (fast waves at > 20ω{sub ci}) may be an attractive option for driving efficient off-axis current drive during non-inductive tokamak operation for DIII-D, ITER and DEMO. For DIII-D scenarios, the ray tracing code, GENRAY, has been extensively used to study helicon current drive efficiency and location as a function of many plasma parameters. The full wave code, AORSA, which is applicable to arbitrary Larmor radius and can resolve arbitrary ion cyclotron harmonic order, has been recently used to validate the ray tracing technique at these high cyclotron harmonics. If the SOL is ignored,more » it will be shown that the GENRAY and AORSA calculated current drive profiles are comparable for the envisioned high beta advanced scenarios for DIII-D, where there is high single pass absorption due to electron Landau damping and minimal ion damping. AORSA is also been used to estimate possible SOL effects on helicon current drive coupling and SOL absorption due to collisional and slow wave effects.« less

Combining analysis with optimization at Langley Research Center. An evolutionary process

NASA Technical Reports Server (NTRS)

Rogers, J. L., Jr.

1982-01-01

The evolutionary process of combining analysis and optimization codes was traced with a view toward providing insight into the long term goal of developing the methodology for an integrated, multidisciplinary software system for the concurrent analysis and optimization of aerospace structures. It was traced along the lines of strength sizing, concurrent strength and flutter sizing, and general optimization to define a near-term goal for combining analysis and optimization codes. Development of a modular software system combining general-purpose, state-of-the-art, production-level analysis computer programs for structures, aerodynamics, and aeroelasticity with a state-of-the-art optimization program is required. Incorporation of a modular and flexible structural optimization software system into a state-of-the-art finite element analysis computer program will facilitate this effort. This effort results in the software system used that is controlled with a special-purpose language, communicates with a data management system, and is easily modified for adding new programs and capabilities. A 337 degree-of-freedom finite element model is used in verifying the accuracy of this system.

A model of polarized-beam AGS in the ray-tracing code Zgoubi

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

Meot, F.; Ahrens, L.; Brown, K.

A model of the Alternating Gradient Synchrotron, based on the AGS snapramps, has been developed in the stepwise ray-tracing code Zgoubi. It has been used over the past 5 years in a number of accelerator studies aimed at enhancing RHIC proton beam polarization. It is also used to study and optimize proton and Helion beam polarization in view of future RHIC and eRHIC programs. The AGS model in Zgoubi is operational on-line via three different applications, ’ZgoubiFromSnaprampCmd’, ’AgsZgoubiModel’ and ’AgsModelViewer’, with the latter two essentially interfaces to the former which is the actual model ’engine’. All three commands are availablemore » from the controls system application launcher in the AGS ’StartUp’ menu, or from eponymous commands on shell terminals. Main aspects of the model and of its operation are presented in this technical note, brief excerpts from various studies performed so far are given for illustration, means and methods entering in ZgoubiFromSnaprampCmd are developed further in appendix.« less

Using AORSA to simulate helicon waves in DIII-D

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

Lau, Cornwall H; Jaeger, E. F.; Bertelli, Nicola

2015-01-01

Recent efforts have shown that helicon waves (fast waves at >20 omega(ci)) may be an attractive option for driving efficient off-axis current drive during non-inductive tokamak operation for DIII-D, ITER and DEMO. For DIII-D scenarios, the ray tracing code, GENRAY, has been extensively used to study helicon current drive efficiency and location as a function of many plasma parameters. The full wave code, AORSA, which is applicable to arbitrary Larmor radius and can resolve arbitrary ion cyclotron harmonic order, has been recently used to validate the ray tracing technique at these high cyclotron harmonics. If the SOL is ignored, itmore » will be shown that the GENRAY and AORSA calculated current drive profiles are comparable for the envisioned high beta advanced scenarios for DIII-D, where there is high single pass absorption due to electron Landau damping and minimal ion damping. AORSA is also been used to estimate possible SOL effects on helicon current drive coupling and SOL absorption due to collisional and slow wave effects.« less

Development of a NRSE Spectrometer with the Help of McStas - Application to the Design of Present and Future Instruments

NASA Astrophysics Data System (ADS)

Kredler, L.; Häußler, W.; Martin, N.; Böni, P.

The flux is still a major limiting factor in neutron research. For instruments being supplied by cold neutrons using neutron guides, both at present steady-state and at new spallation neutron sources, it is therefore important to optimize the instrumental setup and the neutron guidance. Optimization of neutron guide geometry and of the instrument itself can be performed by numerical ray-tracing simulations using existing open-access codes. In this paper, we discuss how such Monte Carlo simulations have been employed in order to plan improvements of the Neutron Resonant Spin Echo spectrometer RESEDA (FRM II, Germany) as well as the neutron guides before and within the instrument. The essential components have been represented with the help of the McStas ray-tracing package. The expected intensity has been tested by means of several virtual detectors, implemented in the simulation code. Comparison between simulations and preliminary measurements results shows good agreement and demonstrates the reliability of the numerical approach. These results will be taken into account in the planning of new components installed in the guide system.

Case ascertainment and estimated incidence of drug-induced long-QT syndrome: study in Southwest France

PubMed Central

Molokhia, Mariam; Pathak, Atul; Lapeyre-Mestre, Maryse; Caturla, Laetitia; Montastruc, Jean Louis; McKeigue, Paul

2008-01-01

AIMS The aim of this study was to investigate the incidence and reporting rate of drug-induced long-QT syndrome (LQTS) in France [defined by evidence of torsades de pointes (TdP), QT prolongation and exposure to a relevant drug] and to assess feasibility of case collection for drug-induced LQTS. METHODS A retrospective population-based study was carried out in Southwest France in five institutions: three main hospitals, one private clinic and one cardiac emergency unit, searched from 1 January 1999 to 1 January 2005 (population coverage of 614 000). The study population consisted of 861 cases with International Classification of Diseases-10 diagnostic codes for ventricular tachycardia (I147.2), ventricular fibrillation (I149.0) and sudden cardiac death (I146.1) from hospital discharge summaries, supplemented by cases reported to national or regional pharmacovigilance systems, and voluntary reporting by physicians, validated according to internationally defined criteria for drug-induced LQTS. RESULTS Of 861 patients coded with arrhythmias or sudden cardiac death, there were 40 confirmed surviving acquired cases of drug-induced LQTS. We estimated that the incidence of those who survive to reach hospital drug-induced LQTS is approximately 10.9 per million annually in France (95% confidence interval 7.8, 14.8). CONCLUSIONS Many cases of drug-induced LQTS may not survive before they reach hospital, as the reporting rate for drug-induced LQTS identified through the cardiology records and also reported to pharmacovigilance systems for the Midi-Pyrenees area is 3/40 (7.5%). Using the methods outlined it is possible to assemble cases to study genetic susceptibility to drug-induced LQTS and adapt these methods more widely. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Drug-induced long-QT syndrome (LQTS) is a potentially fatal condition that has led to a number of postmarketing withdrawals in recent years. However, many cases may not survive long enough to reach hospital, and only a small proportion are reported to pharmacovigilance agencies. The extent to which genetic determinants of susceptibility to LQTS are specific to particular drugs, or common to several classes of drug, remains to be determined. WHAT THIS STUDY ADDS We estimated population prevalence of drug-induced LQTS in the Midi-Pyrenees region, southwest France, using five different institutions and assessed feasibility of tracing potential cases (in addition to pharmacovigilance data), using hospital data and rigorous case definition.These methods can be adapted to a wider region, used to augment pharmacovigilance reporting, and offer researchers the opportunity to study genetic susceptibility to drug-induced LQTS. PMID:18637888

Prevalence of virulence genes in Escherichia coli strains isolated from Romanian adult urinary tract infection cases.

PubMed

Usein, C R; Damian, M; Tatu-Chitoiu, D; Capusa, C; Fagaras, R; Tudorache, D; Nica, M; Le Bouguénec, C

2001-01-01

A total of 78 E. coli strains isolated from adults with different types of urinary tract infections were screened by polymerase chain reaction for prevalence of genetic regions coding for virulence factors. The targeted genetic determinants were those coding for type 1 fimbriae (fimH), pili associated with pyelonephritis (pap), S and F1C fimbriae (sfa and foc), afimbrial adhesins (afa), hemolysin (hly), cytotoxic necrotizing factor (cnf), aerobactin (aer). Among the studied strains, the prevalence of genes coding for fimbrial adhesive systems was 86%, 36%, and 23% for fimH, pap, and sfa/foc,respectively. The operons coding for Afa afimbrial adhesins were identified in 14% of strains. The hly and cnf genes coding for toxins were amplified in 23% and 13% of strains, respectively. A prevalence of 54% was found for the aer gene. The various combinations of detected genes were designated as virulence patterns. The strains isolated from the hospitalized patients displayed a greater number of virulence genes and a diversity of gene associations compared to the strains isolated from the ambulatory subjects. A rapid assessment of the bacterial pathogenicity characteristics may contribute to a better medical approach of the patients with urinary tract infections.

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

Platania, P., E-mail: platania@ifp.cnr.it; Figini, L.; Farina, D.

The purpose of this work is the optical modeling and physical performances evaluations of the JT-60SA ECRF launcher system. The beams have been simulated with the electromagnetic code GRASP® and used as input for ECCD calculations performed with the beam tracing code GRAY, capable of modeling propagation, absorption and current drive of an EC Gaussion beam with general astigmatism. Full details of the optical analysis has been taken into account to model the launched beams. Inductive and advanced reference scenarios has been analysed for physical evaluations in the full poloidal and toroidal steering ranges for two slightly different layouts ofmore » the launcher system.« less

Analysis Of The Boeing FEL Mirror Measurements

NASA Astrophysics Data System (ADS)

Knapp, Charles E.; Viswanathan, Vriddhachalam K.; Appert, Quentin D.

1989-07-01

The aberrations have been measured for the finished mirrors that are part of the Burst Mode ring resonator of the Free Electron Laser (FEL) being constructed at the Boeing Aerospace Company in Seattle, Washington. This paper presents analysis of these measurements using the GLAD code, a diffraction ray-tracing code. The diffraction losses within the resonator due to the aberrations are presented. The analysis was conducted in two different modes, a paraxial approximation and a full 3-D calculation, and good agreement between the two approaches is shown. Finally, a proposed solution to the problems caused by the aberrations is presented and analyzed.

Learning about the Benetic Code via Programming: Representing the Process of Translation.

ERIC Educational Resources Information Center

Ploger, Don

1991-01-01

This study examined the representations that a 16-year-old student made using the flexible computer system, "Boxer," in learning the genetic code. Results indicated that programing made it easier to build and explore flexible and useful representations and encouraged interdisciplinary collaboration between mathematics and biology…

RELAP-7 Code Assessment Plan and Requirement Traceability Matrix

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

Yoo, Junsoo; Choi, Yong-joon; Smith, Curtis L.

2016-10-01

The RELAP-7, a safety analysis code for nuclear reactor system, is under development at Idaho National Laboratory (INL). Overall, the code development is directed towards leveraging the advancements in computer science technology, numerical solution methods and physical models over the last decades. Recently, INL has also been putting an effort to establish the code assessment plan, which aims to ensure an improved final product quality through the RELAP-7 development process. The ultimate goal of this plan is to propose a suitable way to systematically assess the wide range of software requirements for RELAP-7, including the software design, user interface, andmore » technical requirements, etc. To this end, we first survey the literature (i.e., international/domestic reports, research articles) addressing the desirable features generally required for advanced nuclear system safety analysis codes. In addition, the V&V (verification and validation) efforts as well as the legacy issues of several recently-developed codes (e.g., RELAP5-3D, TRACE V5.0) are investigated. Lastly, this paper outlines the Requirement Traceability Matrix (RTM) for RELAP-7 which can be used to systematically evaluate and identify the code development process and its present capability.« less

Theory of epigenetic coding.

PubMed

Elder, D

1984-06-07

The logic of genetic control of development may be based on a binary epigenetic code. This paper revises the author's previous scheme dealing with the numerology of annelid metamerism in these terms. Certain features of the code had been deduced to be combinatorial, others not. This paradoxical contrast is resolved here by the interpretation that these features relate to different operations of the code; the combinatiorial to coding identity of units, the non-combinatorial to coding production of units. Consideration of a second paradox in the theory of epigenetic coding leads to a new solution which further provides a basis for epimorphic regeneration, and may in particular throw light on the "regeneration-duplication" phenomenon. A possible test of the model is also put forward.

Retrieval of trace gas concentrations over Summit Station, Greenland using moderate-resolution spectral infrared radiances

NASA Astrophysics Data System (ADS)

Bahramvash Shams, S.; Walden, V. P.; Turner, D. D.

2017-12-01

Measurements of trace gases at high temporal resolution are important for understanding variations and trends at high latitudes. Trace gases over Greenland can be influenced by both long-range transport from pollution sources as well as local chemical processes. Satellite retrievals are an important data source in the polar regions, but accurate ground-based measurements are needed for proper validation, especially in data sparse regions. A moderate-resolution (0.5 cm-1) Fourier transform infrared spectrometer (FTIR), the Polar Atmospheric Emitted Radiance Interferometer (P-AERI), has been operated at Summit Station, Greenland as part of the ICECAPS project since 2010. In this study, trace gas concentrations, including ozone, nitrous oxide, and methane are retrieved using different optimal estimation retrieval codes. We first present results of retrieved gases using synthetic spectra (from a radiative transfer model) that mimic P-AERI measurements to evaluate systematic errors in the inverse models. We also retrieve time series of trace gas concentrations during periods of clear skies over Summit. We investigate the amount of vertical information that can be obtained with moderate resolution spectra for each of the trace gases, and also the impact of the seasonal variation of atmospheric water vapor on the retrievals. Data from surface observations and ozonesondes obtained by the NOAA Global Monitoring Division are used to improve the retrievals and as validation.

SWVRHC: On Its Own and Going Strong.

ERIC Educational Resources Information Center

Appalachia, 1985

1985-01-01

Traces Southern West Virginia Regional Health Council's decade of delivering/linking cradle-to-grave health services for 500,000 rural residents. Describes microwave communications radio network; clinics; services in family planning, genetic counseling, prenatal care, maternal/child care, nutrition, heart/respiratory disease screening, renal…

Heuristic rules embedded genetic algorithm for in-core fuel management optimization

NASA Astrophysics Data System (ADS)

Alim, Fatih

The objective of this study was to develop a unique methodology and a practical tool for designing loading pattern (LP) and burnable poison (BP) pattern for a given Pressurized Water Reactor (PWR) core. Because of the large number of possible combinations for the fuel assembly (FA) loading in the core, the design of the core configuration is a complex optimization problem. It requires finding an optimal FA arrangement and BP placement in order to achieve maximum cycle length while satisfying the safety constraints. Genetic Algorithms (GA) have been already used to solve this problem for LP optimization for both PWR and Boiling Water Reactor (BWR). The GA, which is a stochastic method works with a group of solutions and uses random variables to make decisions. Based on the theories of evaluation, the GA involves natural selection and reproduction of the individuals in the population for the next generation. The GA works by creating an initial population, evaluating it, and then improving the population by using the evaluation operators. To solve this optimization problem, a LP optimization package, GARCO (Genetic Algorithm Reactor Code Optimization) code is developed in the framework of this thesis. This code is applicable for all types of PWR cores having different geometries and structures with an unlimited number of FA types in the inventory. To reach this goal, an innovative GA is developed by modifying the classical representation of the genotype. To obtain the best result in a shorter time, not only the representation is changed but also the algorithm is changed to use in-core fuel management heuristics rules. The improved GA code was tested to demonstrate and verify the advantages of the new enhancements. The developed methodology is explained in this thesis and preliminary results are shown for the VVER-1000 reactor hexagonal geometry core and the TMI-1 PWR. The improved GA code was tested to verify the advantages of new enhancements. The core physics code used for VVER in this research is Moby-Dick, which was developed to analyze the VVER by SKODA Inc. The SIMULATE-3 code, which is an advanced two-group nodal code, is used to analyze the TMI-1.

Simulation of a main steam line break with steam generator tube rupture using trace

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

Gallardo, S.; Querol, A.; Verdu, G.

A simulation of the OECD/NEA ROSA-2 Project Test 5 was made with the thermal-hydraulic code TRACE5. Test 5 performed in the Large Scale Test Facility (LSTF) reproduced a Main Steam Line Break (MSLB) with a Steam Generator Tube Rupture (SGTR) in a Pressurized Water Reactor (PWR). The result of these simultaneous breaks is a depressurization in the secondary and primary system in loop B because both systems are connected through the SGTR. Good approximation was obtained between TRACE5 results and experimental data. TRACE5 reproduces qualitatively the phenomena that occur in this transient: primary pressure falls after the break, stagnation ofmore » the pressure after the opening of the relief valve of the intact steam generator, the pressure falls after the two openings of the PORV and the recovery of the liquid level in the pressurizer after each closure of the PORV. Furthermore, a sensitivity analysis has been performed to know the effect of varying the High Pressure Injection (HPI) flow rate in both loops on the system pressures evolution. (authors)« less

Privacy rules for DNA databanks. Protecting coded 'future diaries'.

PubMed

Annas, G J

1993-11-17

In privacy terms, genetic information is like medical information. But the information contained in the DNA molecule itself is more sensitive because it contains an individual's probabilistic "future diary," is written in a code that has only partially been broken, and contains information about an individual's parents, siblings, and children. Current rules for protecting the privacy of medical information cannot protect either genetic information or identifiable DNA samples stored in DNA databanks. A review of the legal and public policy rationales for protecting genetic privacy suggests that specific enforceable privacy rules for DNA databanks are needed. Four preliminary rules are proposed to govern the creation of DNA databanks, the collection of DNA samples for storage, limits on the use of information derived from the samples, and continuing obligations to those whose DNA samples are in the databanks.

The distribution of mitochondrial DNA haplogroup H in southern Iberia indicates ancient human genetic exchanges along the western edge of the Mediterranean.

PubMed

Hernández, Candela L; Dugoujon, Jean M; Novelletto, Andrea; Rodríguez, Juan N; Cuesta, Pedro; Calderón, Rosario

2017-05-19

The structure of haplogroup H reveals significant differences between the western and eastern edges of the Mediterranean, as well as between the northern and southern regions. Human populations along the westernmost Mediterranean coasts, which were settled by individuals from two continents separated by a relatively narrow body of water, show the highest frequencies of mitochondrial haplogroup H. These characteristics permit the analysis of ancient migrations between both shores, which may have occurred via primitive sea crafts and early seafaring. We collected a sample of 750 autochthonous people from the southern Iberian Peninsula (Andalusians from Huelva and Granada provinces). We performed a high-resolution analysis of haplogroup H by control region sequencing and coding SNP screening of the 337 individuals harboring this maternal marker. Our results were compared with those of a wide panel of populations, including individuals from Iberia, the Maghreb, and other regions around the Mediterranean, collected from the literature. Both Andalusian subpopulations showed a typical western European profile for the internal composition of clade H, but eastern Andalusians from Granada also revealed interesting traces from the eastern Mediterranean. The basal nodes of the most frequent H sub-haplogroups, H1 and H3, harbored many individuals of Iberian and Maghrebian origins. Derived haplotypes were found in both regions; haplotypes were shared far more frequently between Andalusia and Morocco than between Andalusia and the rest of the Maghreb. These and previous results indicate intense, ancient and sustained contact among populations on both sides of the Mediterranean. Our genetic data on mtDNA diversity, combined with corresponding archaeological similarities, provide support for arguments favoring prehistoric bonds with a genetic legacy traceable in extant populations. Furthermore, the results presented here indicate that the Strait of Gibraltar and the adjacent Alboran Sea, which have often been assumed to be an insurmountable geographic barrier in prehistory, served as a frequently traveled route between continents.

Traces of archaic mitochondrial lineages persist in Austronesian-speaking Formosan populations.

PubMed

Trejaut, Jean A; Kivisild, Toomas; Loo, Jun Hun; Lee, Chien Liang; He, Chun Lin; Hsu, Chia Jung; Lee, Zheng Yan; Li, Zheng Yuan; Lin, Marie

2005-08-01

Genetic affinities between aboriginal Taiwanese and populations from Oceania and Southeast Asia have previously been explored through analyses of mitochondrial DNA (mtDNA), Y chromosomal DNA, and human leukocyte antigen loci. Recent genetic studies have supported the "slow boat" and "entangled bank" models according to which the Polynesian migration can be seen as an expansion from Melanesia without any major direct genetic thread leading back to its initiation from Taiwan. We assessed mtDNA variation in 640 individuals from nine tribes of the central mountain ranges and east coast regions of Taiwan. In contrast to the Han populations, the tribes showed a low frequency of haplogroups D4 and G, and an absence of haplogroups A, C, Z, M9, and M10. Also, more than 85% of the maternal lineages were nested within haplogroups B4, B5a, F1a, F3b, E, and M7. Although indicating a common origin of the populations of insular Southeast Asia and Oceania, most mtDNA lineages in Taiwanese aboriginal populations are grouped separately from those found in China and the Taiwan general (Han) population, suggesting a prevalence in the Taiwanese aboriginal gene pool of its initial late Pleistocene settlers. Interestingly, from complete mtDNA sequencing information, most B4a lineages were associated with three coding region substitutions, defining a new subclade, B4a1a, that endorses the origin of Polynesian migration from Taiwan. Coalescence times of B4a1a were 13.2 +/- 3.8 thousand years (or 9.3 +/- 2.5 thousand years in Papuans and Polynesians). Considering the lack of a common specific Y chromosomal element shared by the Taiwanese aboriginals and Polynesians, the mtDNA evidence provided here is also consistent with the suggestion that the proto-Oceanic societies would have been mainly matrilocal.

SEQassembly: A Practical Tools Program for Coding Sequences Splicing

NASA Astrophysics Data System (ADS)

Lee, Hongbin; Yang, Hang; Fu, Lei; Qin, Long; Li, Huili; He, Feng; Wang, Bo; Wu, Xiaoming

CDS (Coding Sequences) is a portion of mRNA sequences, which are composed by a number of exon sequence segments. The construction of CDS sequence is important for profound genetic analysis such as genotyping. A program in MATLAB environment is presented, which can process batch of samples sequences into code segments under the guide of reference exon models, and splice these code segments of same sample source into CDS according to the exon order in queue file. This program is useful in transcriptional polymorphism detection and gene function study.

Developing and validating trace fear conditioning protocols in C57BL/6 mice.

PubMed

Burman, Michael A; Simmons, Cassandra A; Hughes, Miles; Lei, Lei

2014-01-30

Classical fear conditioning is commonly used to study the biology of fear, anxiety and memory. Previous research demonstrated that delay conditioning requires a neural circuit involving the amygdala, but not usually the hippocampus. Trace and contextual fear conditioning require the amygdala and hippocampus. While these paradigms were developed primarily using rat models, they are increasingly being used in mice. The current studies develop trace fear conditioning and control paradigms to allow for the assessment of trace and delay fear conditioning in C57BL/6N mice. Our initial protocol yielded clear delay and contextual conditioning. However, trace conditioning failed to differentiate from an unpaired group and was not hippocampus-dependent. These results suggested that the protocol needed to be modified to specifically accommodate trace conditioning the mice. In order to reduce unconditioned freezing and increase learning, the final protocol was developed by decreasing the intensity of the tone and by increasing the inter-trial interval. Our final protocol produced trace conditioned freezing that was significantly greater than that followed unpaired stimulus exposure and was disrupted by hippocampus lesions. A review of the literature produced 90 articles using trace conditioning in mice. Few of those articles used any kind of behavioral control group, which is required to rule out non-associative factors causing fearful behavior. Fewer used unpaired groups involving tones and shocks within a session, which is the optimal control group. Our final trace conditioning protocol can be used in future studies examining genetically modified C57BL/6N mice. Copyright © 2013 Elsevier B.V. All rights reserved.

Developing and Validating Trace Fear Conditioning Protocols in C57BL/6 Mice

PubMed Central

Burman, Michael A; Simmons, Cassandra A; Hughes, Miles; Lei, Lei

2013-01-01

Background Classical fear conditioning is commonly used to study the biology of fear, anxiety and memory. Previous research demonstrated that delay conditioning requires a neural circuit involving the amygdala, but not usually the hippocampus. Trace and contextual fear conditioning require the amygdala and hippocampus. While these paradigms were developed primarily using rat models, they are increasingly being used in mice. New Method The current studies develop trace fear conditioning and control paradigms to allow for the assessment of trace and delay fear conditioning in C57BL/6N mice. Our initial protocol yielded clear delay and contextual conditioning. However, trace conditioning failed to differentiate from an unpaired group and was not hippocampus-dependent. These results suggested that the protocol needed to be modified to specifically accommodate trace conditioning the mice. In order to reduce unconditioned freezing and increase learning, the final protocol was developed by decreasing the intensity of the tone and by increasing the inter-trial interval. Results Our final protocol produced trace conditioned freezing that was significantly greater than that followed unpaired stimulus exposure and was disrupted by hippocampus lesions. Comparison with Existing Methods A review of the literature produced 90 articles using trace conditioning in mice. Few of those articles used any kind of behavioral control group, which is required to rule out non-associative factors causing fearful behavior. Fewer used unpaired groups involving tones and shocks within a session, which is the optimal control group. Conclusions Our final trace conditioning protocol can be used in future studies examining genetically modified C57BL/6N mice. PMID:24269252

Teaching Molecular Biology with Microcomputers.

ERIC Educational Resources Information Center

Reiss, Rebecca; Jameson, David

1984-01-01

Describes a series of computer programs that use simulation and gaming techniques to present the basic principles of the central dogma of molecular genetics, mutation, and the genetic code. A history of discoveries in molecular biology is presented and the evolution of these computer assisted instructional programs is described. (MBR)

Scientific rationality, uncertainty and the governance of human genetics: an interview study with researchers at deCODE genetics.

PubMed

Hjörleifsson, Stefán; Schei, Edvin

2006-07-01

Technology development in human genetics is fraught with uncertainty, controversy and unresolved moral issues, and industry scientists are sometimes accused of neglecting the implications of their work. The present study was carried out to elicit industry scientists' reflections on the relationship between commercial, scientific and ethical dimensions of present day genetics and the resources needed for robust governance of new technologies. Interviewing scientists of the company deCODE genetics in Iceland, we found that in spite of optimism, the informants revealed ambiguity and uncertainty concerning the use of human genetic technologies for the prevention of common diseases. They concurred that uncritical marketing of scientific success might cause exaggerated public expectations of health benefits from genetics, with the risk of backfiring and causing resistance to genetics in the population. On the other hand, the scientists did not address dilemmas arising from the commercial nature of their own employer. Although the scientists tended to describe public fear as irrational, they identified issues where scepticism might be well founded and explored examples where they, despite expert knowledge, held ambiguous or tentative personal views on the use of predictive genetic technologies. The rationality of science was not seen as sufficient to ensure beneficial governance of new technologies. The reflexivity and suspension of judgement demonstrated in the interviews exemplify productive features of moral deliberation in complex situations. Scientists should take part in dialogues concerning the governance of genetic technologies, acknowledge any vested interests, and use their expertise to highlight, not conceal the technical and moral complexity involved.

Enhanced genetic analysis of single human bioparticles recovered by simplified micromanipulation from forensic 'touch DNA' evidence.

PubMed

Farash, Katherine; Hanson, Erin K; Ballantyne, Jack

2015-03-09

DNA profiles can be obtained from 'touch DNA' evidence, which comprises microscopic traces of human biological material. Current methods for the recovery of trace DNA employ cotton swabs or adhesive tape to sample an area of interest. However, such a 'blind-swabbing' approach will co-sample cellular material from the different individuals, even if the individuals' cells are located in geographically distinct locations on the item. Thus, some of the DNA mixtures encountered in touch DNA samples are artificially created by the swabbing itself. In some instances, a victim's DNA may be found in significant excess thus masking any potential perpetrator's DNA. In order to circumvent the challenges with standard recovery and analysis methods, we have developed a lower cost, 'smart analysis' method that results in enhanced genetic analysis of touch DNA evidence. We describe an optimized and efficient micromanipulation recovery strategy for the collection of bio-particles present in touch DNA samples, as well as an enhanced amplification strategy involving a one-step 5 µl microvolume lysis/STR amplification to permit the recovery of STR profiles from the bio-particle donor(s). The use of individual or few (i.e., "clumps") bioparticles results in the ability to obtain single source profiles. These procedures represent alternative enhanced techniques for the isolation and analysis of single bioparticles from forensic touch DNA evidence. While not necessary in every forensic investigation, the method could be highly beneficial for the recovery of a single source perpetrator DNA profile in cases involving physical assault (e.g., strangulation) that may not be possible using standard analysis techniques. Additionally, the strategies developed here offer an opportunity to obtain genetic information at the single cell level from a variety of other non-forensic trace biological material.

Identification of Genetic Variation on the Horse Y Chromosome and the Tracing of Male Founder Lineages in Modern Breeds

PubMed Central

Wallner, Barbara; Vogl, Claus; Shukla, Priyank; Burgstaller, Joerg P.; Druml, Thomas; Brem, Gottfried

2013-01-01

The paternally inherited Y chromosome displays the population genetic history of males. While modern domestic horses (Equus caballus) exhibit abundant diversity within maternally inherited mitochondrial DNA, no significant Y-chromosomal sequence diversity has been detected. We used high throughput sequencing technology to identify the first polymorphic Y-chromosomal markers useful for tracing paternal lines. The nucleotide variability of the modern horse Y chromosome is extremely low, resulting in six haplotypes (HT), all clearly distinct from the Przewalski horse (E. przewalskii). The most widespread HT1 is ancestral and the other five haplotypes apparently arose on the background of HT1 by mutation or gene conversion after domestication. Two haplotypes (HT2 and HT3) are widely distributed at high frequencies among modern European horse breeds. Using pedigree information, we trace the distribution of Y-haplotype diversity to particular founders. The mutation leading to HT3 occurred in the germline of the famous English Thoroughbred stallion “Eclipse” or his son or grandson and its prevalence demonstrates the influence of this popular paternal line on modern sport horse breeds. The pervasive introgression of Thoroughbred stallions during the last 200 years to refine autochthonous breeds has strongly affected the distribution of Y-chromosomal variation in modern horse breeds and has led to the replacement of autochthonous Y chromosomes. Only a few northern European breeds bear unique variants at high frequencies or fixed within but not shared among breeds. Our Y-chromosomal data complement the well established mtDNA lineages and document the male side of the genetic history of modern horse breeds and breeding practices. PMID:23573227

Tracking illegal small arms traffic across U.S. borders through the implementation of firearm microstamping to small arms and small arms exports

NASA Astrophysics Data System (ADS)

Lizotte, Todd E.; Ohar, Orest P.

2009-05-01

At a border security conference in August 2008, Michael Sullivan, acting director of Bureau of Alcohol, Tobacco, Firearms and Explosives stated that, "Nearly all illegal firearms (90% to 95%) seized in Mexico come from the United States"[1]. When firearms are recovered at a crime scene, the firearms can be traced providing specific details on illegal firearm dealers or straw purchasers within the United States. Criminals or narco terrorist groups target US dealers to source firearms for drug cartels in Mexico and South America. Joint law enforcement programs between the US and Mexico law enforcement have been effective, however, in most cases the firearms that are seized are only a small fraction of the firearms trafficked across the United States border. A technology called Microstamping, when applied to newly manufactured firearms will provide further opportunities for tracing illegal firearms for law enforcement in the United States and across the globe. Microstamping is a patented technology and trace solution where intentional tooling marks are formed or micromachined onto firearms interior surfaces that come into contact or impact the surfaces of cartridge casings. The intentional tooling marks can take the form of alphanumeric codes or encoded geometric codes, such as a barcode. As the firearm is discharged the intentional tooling marks transfer a code to the cartridge casing before it is ejected out of the firearm. When recovered at the scene of an incident, the Microstamped cartridge can indentify a specific firearm, without the need to recover that firearm. Microstamping provides critical intelligence for use in border security operations and cross border violent drug related crime investigations. This paper will explain the key attributes of microstamping technology; including its potential benefits in border security operations and how data gathered from the technique can be used in geospatial information systems to identify illicit firearm sources, trafficking routes, as well as spatial and temporal mapping of narco-terrorist movements on either side of the border.

Efficacy of a web-based intelligent tutoring system for communicating genetic risk of breast cancer: a fuzzy-trace theory approach.

PubMed

Wolfe, Christopher R; Reyna, Valerie F; Widmer, Colin L; Cedillos, Elizabeth M; Fisher, Christopher R; Brust-Renck, Priscila G; Weil, Audrey M

2015-01-01

. Many healthy women consider genetic testing for breast cancer risk, yet BRCA testing issues are complex. . To determine whether an intelligent tutor, BRCA Gist, grounded in fuzzy-trace theory (FTT), increases gist comprehension and knowledge about genetic testing for breast cancer risk, improving decision making. . In 2 experiments, 410 healthy undergraduate women were randomly assigned to 1 of 3 groups: an online module using a Web-based tutoring system (BRCA Gist) that uses artificial intelligence technology, a second group read highly similar content from the National Cancer Institute (NCI) Web site, and a third that completed an unrelated tutorial. . BRCA Gist applied FTT and was designed to help participants develop gist comprehension of topics relevant to decisions about BRCA genetic testing, including how breast cancer spreads, inherited genetic mutations, and base rates. . We measured content knowledge, gist comprehension of decision-relevant information, interest in testing, and genetic risk and testing judgments. . Control knowledge scores ranged from 54% to 56%, NCI improved significantly to 65% and 70%, and BRCA Gist improved significantly more to 75% and 77%, P < 0.0001. BRCA Gist scored higher on gist comprehension than NCI and control, P < 0.0001. Control genetic risk-assessment mean was 48% correct; BRCA Gist (61%) and NCI (56%) were significantly higher, P < 0.0001. BRCA Gist participants recommended less testing for women without risk factors (not good candidates; 24% and 19%) than controls (50%, both experiments) and NCI (32%), experiment 2, P < 0.0001. BRCA Gist testing interest was lower than in controls, P < 0.0001. . BRCA Gist has not been tested with older women from diverse groups. . Intelligent tutors, such as BRCA Gist, are scalable, cost-effective ways of helping people understand complex issues, improving decision making. © The Author(s) 2014.

A novel neutron energy spectrum unfolding code using particle swarm optimization

NASA Astrophysics Data System (ADS)

Shahabinejad, H.; Sohrabpour, M.

2017-07-01

A novel neutron Spectrum Deconvolution using Particle Swarm Optimization (SDPSO) code has been developed to unfold the neutron spectrum from a pulse height distribution and a response matrix. The Particle Swarm Optimization (PSO) imitates the bird flocks social behavior to solve complex optimization problems. The results of the SDPSO code have been compared with those of the standard spectra and recently published Two-steps Genetic Algorithm Spectrum Unfolding (TGASU) code. The TGASU code have been previously compared with the other codes such as MAXED, GRAVEL, FERDOR and GAMCD and shown to be more accurate than the previous codes. The results of the SDPSO code have been demonstrated to match well with those of the TGASU code for both under determined and over-determined problems. In addition the SDPSO has been shown to be nearly two times faster than the TGASU code.

ASTRORAY: General relativistic polarized radiative transfer code

NASA Astrophysics Data System (ADS)

Shcherbakov, Roman V.

2014-07-01

ASTRORAY employs a method of ray tracing and performs polarized radiative transfer of (cyclo-)synchrotron radiation. The radiative transfer is conducted in curved space-time near rotating black holes described by Kerr-Schild metric. Three-dimensional general relativistic magneto hydrodynamic (3D GRMHD) simulations, in particular performed with variations of the HARM code, serve as an input to ASTRORAY. The code has been applied to reproduce the sub-mm synchrotron bump in the spectrum of Sgr A*, and to test the detectability of quasi-periodic oscillations in its light curve. ASTRORAY can be readily applied to model radio/sub-mm polarized spectra of jets and cores of other low-luminosity active galactic nuclei. For example, ASTRORAY is uniquely suitable to self-consistently model Faraday rotation measure and circular polarization fraction in jets.

Encoding lexical tones in jTRACE: a simulation of monosyllabic spoken word recognition in Mandarin Chinese.

PubMed

Shuai, Lan; Malins, Jeffrey G

2017-02-01

Despite its prevalence as one of the most highly influential models of spoken word recognition, the TRACE model has yet to be extended to consider tonal languages such as Mandarin Chinese. A key reason for this is that the model in its current state does not encode lexical tone. In this report, we present a modified version of the jTRACE model in which we borrowed on its existing architecture to code for Mandarin phonemes and tones. Units are coded in a way that is meant to capture the similarity in timing of access to vowel and tone information that has been observed in previous studies of Mandarin spoken word recognition. We validated the model by first simulating a recent experiment that had used the visual world paradigm to investigate how native Mandarin speakers process monosyllabic Mandarin words (Malins & Joanisse, 2010). We then subsequently simulated two psycholinguistic phenomena: (1) differences in the timing of resolution of tonal contrast pairs, and (2) the interaction between syllable frequency and tonal probability. In all cases, the model gave rise to results comparable to those of published data with human subjects, suggesting that it is a viable working model of spoken word recognition in Mandarin. It is our hope that this tool will be of use to practitioners studying the psycholinguistics of Mandarin Chinese and will help inspire similar models for other tonal languages, such as Cantonese and Thai.

Three-dimensional Monte Carlo calculation of atmospheric thermal heating rates

NASA Astrophysics Data System (ADS)

Klinger, Carolin; Mayer, Bernhard

2014-09-01

We present a fast Monte Carlo method for thermal heating and cooling rates in three-dimensional atmospheres. These heating/cooling rates are relevant particularly in broken cloud fields. We compare forward and backward photon tracing methods and present new variance reduction methods to speed up the calculations. For this application it turns out that backward tracing is in most cases superior to forward tracing. Since heating rates may be either calculated as the difference between emitted and absorbed power per volume or alternatively from the divergence of the net flux, both approaches have been tested. We found that the absorption/emission method is superior (with respect to computational time for a given uncertainty) if the optical thickness of the grid box under consideration is smaller than about 5 while the net flux divergence may be considerably faster for larger optical thickness. In particular, we describe the following three backward tracing methods: the first and most simple method (EMABS) is based on a random emission of photons in the grid box of interest and a simple backward tracing. Since only those photons which cross the grid box boundaries contribute to the heating rate, this approach behaves poorly for large optical thicknesses which are common in the thermal spectral range. For this reason, the second method (EMABS_OPT) uses a variance reduction technique to improve the distribution of the photons in a way that more photons are started close to the grid box edges and thus contribute to the result which reduces the uncertainty. The third method (DENET) uses the flux divergence approach where - in backward Monte Carlo - all photons contribute to the result, but in particular for small optical thickness the noise becomes large. The three methods have been implemented in MYSTIC (Monte Carlo code for the phYSically correct Tracing of photons In Cloudy atmospheres). All methods are shown to agree within the photon noise with each other and with a discrete ordinate code for a one-dimensional case. Finally a hybrid method is built using a combination of EMABS_OPT and DENET, and application examples are shown. It should be noted that for this application, only little improvement is gained by EMABS_OPT compared to EMABS.

TIME-DEPENDENT MULTI-GROUP MULTI-DIMENSIONAL RELATIVISTIC RADIATIVE TRANSFER CODE BASED ON SPHERICAL HARMONIC DISCRETE ORDINATE METHOD

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

Tominaga, Nozomu; Shibata, Sanshiro; Blinnikov, Sergei I., E-mail: tominaga@konan-u.ac.jp, E-mail: sshibata@post.kek.jp, E-mail: Sergei.Blinnikov@itep.ru

We develop a time-dependent, multi-group, multi-dimensional relativistic radiative transfer code, which is required to numerically investigate radiation from relativistic fluids that are involved in, e.g., gamma-ray bursts and active galactic nuclei. The code is based on the spherical harmonic discrete ordinate method (SHDOM) which evaluates a source function including anisotropic scattering in spherical harmonics and implicitly solves the static radiative transfer equation with ray tracing in discrete ordinates. We implement treatments of time dependence, multi-frequency bins, Lorentz transformation, and elastic Thomson and inelastic Compton scattering to the publicly available SHDOM code. Our code adopts a mixed-frame approach; the source functionmore » is evaluated in the comoving frame, whereas the radiative transfer equation is solved in the laboratory frame. This implementation is validated using various test problems and comparisons with the results from a relativistic Monte Carlo code. These validations confirm that the code correctly calculates the intensity and its evolution in the computational domain. The code enables us to obtain an Eddington tensor that relates the first and third moments of intensity (energy density and radiation pressure) and is frequently used as a closure relation in radiation hydrodynamics calculations.« less

Synthetic Genome Recoding: New genetic codes for new features

PubMed Central

Kuo, James; Stirling, Finn; Lau, Yu Heng; Shulgina, Yekaterina; Way, Jeffrey C.; Silver, Pamela A.

2018-01-01

Full genome recoding, or rewriting codon meaning, through chemical synthesis of entire bacterial chromosomes has become feasible in the past several years. Recoding an organism can impart new properties including non-natural amino acid incorporation, virus resistance, and biocontainment. The estimated cost of construction that includes DNA synthesis, assembly by recombination, and troubleshooting, is now comparable to costs of early stage development of drugs or other high-tech products. Here we discuss several recently published assembly methods and provide some thoughts on the future, including how synthetic efforts might benefit from analysis of natural recoding processes and organisms that use alternative genetic codes. PMID:28983660

Grain Propellant Optimization Using Real Code Genetic Algorithm (RCGA)

NASA Astrophysics Data System (ADS)

Farizi, Muhammad Farraz Al; Oktovianus Bura, Romie; Fajar Junjunan, Soleh; Jihad, Bagus H.

2018-04-01

Grain propellant design is important in rocket motor design. The total impulse and ISP of the rocket motor is influenced by the grain propellant design. One way to get a grain propellant shape that generates the maximum total impulse value is to use the Real Code Genetic Algorithm (RCGA) method. In this paper RCGA is applied to star grain Rx-450. To find burn area of propellant used analytical method. While the combustion chamber pressures are sought with zero-dimensional equations. The optimization result can reach the desired target and increase the total impulse value by 3.3% from the initial design of Rx-450.

Metabolic basis for the self-referential genetic code.

PubMed

Guimarães, Romeu Cardoso

2011-08-01

An investigation of the biosynthesis pathways producing glycine and serine was necessary to clarify an apparent inconsistency between the self-referential model (SRM) for the formation of the genetic code and the model of coevolution of encodings and of amino acid biosynthesis routes. According to the SRM proposal, glycine was the first amino acid encoded, followed by serine. The coevolution model does not state precisely which the first encodings were, only presenting a list of about ten early assignments including the derivation of glycine from serine-this being derived from the glycolysis intermediate glycerate, which reverses the order proposed by the self-referential model. Our search identified the glycine-serine pathway of syntheses based on one-carbon sources, involving activities of the glycine decarboxylase complex and its associated serine hydroxymethyltransferase, which is consistent with the order proposed by the self-referential model and supports its rationale for the origin of the genetic code: protein synthesis was developed inside an early metabolic system, serving the function of a sink of amino acids; the first peptides were glycine-rich and fit for the function of building the early ribonucleoproteins; glycine consumption in proteins drove the fixation of the glycine-serine pathway.

Automated recognition of the pericardium contour on processed CT images using genetic algorithms.

PubMed

Rodrigues, É O; Rodrigues, L O; Oliveira, L S N; Conci, A; Liatsis, P

2017-08-01

This work proposes the use of Genetic Algorithms (GA) in tracing and recognizing the pericardium contour of the human heart using Computed Tomography (CT) images. We assume that each slice of the pericardium can be modelled by an ellipse, the parameters of which need to be optimally determined. An optimal ellipse would be one that closely follows the pericardium contour and, consequently, separates appropriately the epicardial and mediastinal fats of the human heart. Tracing and automatically identifying the pericardium contour aids in medical diagnosis. Usually, this process is done manually or not done at all due to the effort required. Besides, detecting the pericardium may improve previously proposed automated methodologies that separate the two types of fat associated to the human heart. Quantification of these fats provides important health risk marker information, as they are associated with the development of certain cardiovascular pathologies. Finally, we conclude that GA offers satisfiable solutions in a feasible amount of processing time. Copyright © 2017 Elsevier Ltd. All rights reserved.

BioQ: tracing experimental origins in public genomic databases using a novel data provenance model

PubMed Central

Saccone, Scott F.; Quan, Jiaxi; Jones, Peter L.

2012-01-01

Motivation: Public genomic databases, which are often used to guide genetic studies of human disease, are now being applied to genomic medicine through in silico integrative genomics. These databases, however, often lack tools for systematically determining the experimental origins of the data. Results: We introduce a new data provenance model that we have implemented in a public web application, BioQ, for assessing the reliability of the data by systematically tracing its experimental origins to the original subjects and biologics. BioQ allows investigators to both visualize data provenance as well as explore individual elements of experimental process flow using precise tools for detailed data exploration and documentation. It includes a number of human genetic variation databases such as the HapMap and 1000 Genomes projects. Availability and implementation: BioQ is freely available to the public at http://bioq.saclab.net Contact: ssaccone@wustl.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:22426342

Exploring dynamics of molybdate in living animal cells by a genetically encoded FRET nanosensor.

PubMed

Nakanishi, Yoichi; Iida, Syuntaro; Ueoka-Nakanishi, Hanayo; Niimi, Tomoaki; Tomioka, Rie; Maeshima, Masayoshi

2013-01-01

Molybdenum (Mo) is an essential trace element for almost all living organisms including animals. Mo is used as a catalytic center of molybdo-enzymes for oxidation/reduction reactions of carbon, nitrogen, and sulfur metabolism. Whilst living cells are known to import inorganic molybdate oxyanion from the surrounding environment, the in vivo dynamics of cytosolic molybdate remain poorly understood as no appropriate indicator is available for this trace anion. We here describe a genetically encoded Förester-resonance-energy-transfer (FRET)-based nanosensor composed of CFP, YFP and the bacterial molybdate-sensor protein ModE. The nanosensor MolyProbe containing an optimized peptide-linker responded to nanomolar-range molybdate selectively, and increased YFP:CFP fluorescence intensity ratio by up to 109%. By introduction of the nanosensor, we have been able to successfully demonstrate the real-time dynamics of molybdate in living animal cells. Furthermore, time course analyses of the dynamics suggest that novel oxalate-sensitive- and sulfate-resistant- transporter(s) uptake molybdate in a model culture cell.

Detecting multiple DNA human profile from a mosquito blood meal.

PubMed

Rabêlo, K C N; Albuquerque, C M R; Tavares, V B; Santos, S M; Souza, C A; Oliveira, T C; Moura, R R; Brandão, L A C; Crovella, S

2016-08-26

Criminal traces commonly found at crime scenes may present mixtures from two or more individuals. The scene of the crime is important for the collection of various types of traces in order to find the perpetrator of the crime. Thus, we propose that hematophagous mosquitoes found at crime scenes can be used to perform genetic testing of human blood and aid in suspect investigation. The aim of the study was to obtain a single Aedes aegypti mosquito profile from a human DNA mixture containing genetic materials of four individuals. We also determined the effect of blood acquisition time by setting time intervals of 24, 48, and 72 h after the blood meal. STR loci and amelogenin were analyzed, and the results showed that human DNA profiles could be obtained from hematophagous mosquitos at 24 h following the blood meal. It is possible that hematophagous mosquitoes can be used as biological remains at the scene of the crime, and can be used to detect human DNA profiles of up to four individuals.

Supporting Students' Knowledge Transfer in Modeling Activities

ERIC Educational Resources Information Center

Piksööt, Jaanika; Sarapuu, Tago

2014-01-01

This study investigates ways to enhance secondary school students' knowledge transfer in complex science domains by implementing question prompts. Two samples of students applied two web-based models to study molecular genetics--the model of genetic code (n = 258) and translation (n = 245). For each model, the samples were randomly divided into…

Using Economics and Genetics To Produce Leaner Pork.

ERIC Educational Resources Information Center

Welch, Mary A., Ed.

1994-01-01

The booklet describes the STAGES (Swine Testing and Genetic Evaluation System) program developed at Purdue University (Indiana), along with the USDA, National Pork Producers Council and swine breed associations. By selecting breeding stock from a coded catalogue developed by STAGES, producers are able to select the best breeding stock for more…

An Inquiry Activity for Genetics Using Chromosome Mapping.

ERIC Educational Resources Information Center

Leonard, William H.; Snodgrass, George

1982-01-01

Concepts to be developed, objectives, and student instructions are provided for an activity useful as an introduction to or review of Mendelian genetics and sex determination. Universal codes (read by optical scanners at supermarket checkout stands) from soup can labels are used as chromosome maps during the activity. (JN)

DeepNeuron: an open deep learning toolbox for neuron tracing.

PubMed

Zhou, Zhi; Kuo, Hsien-Chi; Peng, Hanchuan; Long, Fuhui

2018-06-06

Reconstructing three-dimensional (3D) morphology of neurons is essential for understanding brain structures and functions. Over the past decades, a number of neuron tracing tools including manual, semiautomatic, and fully automatic approaches have been developed to extract and analyze 3D neuronal structures. Nevertheless, most of them were developed based on coding certain rules to extract and connect structural components of a neuron, showing limited performance on complicated neuron morphology. Recently, deep learning outperforms many other machine learning methods in a wide range of image analysis and computer vision tasks. Here we developed a new Open Source toolbox, DeepNeuron, which uses deep learning networks to learn features and rules from data and trace neuron morphology in light microscopy images. DeepNeuron provides a family of modules to solve basic yet challenging problems in neuron tracing. These problems include but not limited to: (1) detecting neuron signal under different image conditions, (2) connecting neuronal signals into tree(s), (3) pruning and refining tree morphology, (4) quantifying the quality of morphology, and (5) classifying dendrites and axons in real time. We have tested DeepNeuron using light microscopy images including bright-field and confocal images of human and mouse brain, on which DeepNeuron demonstrates robustness and accuracy in neuron tracing.

Comparative modelling of lower hybrid current drive with two launcher designs in the Tore Supra tokamak

NASA Astrophysics Data System (ADS)

Nilsson, E.; Decker, J.; Peysson, Y.; Artaud, J.-F.; Ekedahl, A.; Hillairet, J.; Aniel, T.; Basiuk, V.; Goniche, M.; Imbeaux, F.; Mazon, D.; Sharma, P.

2013-08-01

Fully non-inductive operation with lower hybrid current drive (LHCD) in the Tore Supra tokamak is achieved using either a fully active multijunction (FAM) launcher or a more recent ITER-relevant passive active multijunction (PAM) launcher, or both launchers simultaneously. While both antennas show comparable experimental efficiencies, the analysis of stability properties in long discharges suggest different current profiles. We present comparative modelling of LHCD with the two different launchers to characterize the effect of the respective antenna spectra on the driven current profile. The interpretative modelling of LHCD is carried out using a chain of codes calculating, respectively, the global discharge evolution (tokamak simulator METIS), the spectrum at the antenna mouth (LH coupling code ALOHA), the LH wave propagation (ray-tracing code C3PO), and the distribution function (3D Fokker-Planck code LUKE). Essential aspects of the fast electron dynamics in time, space and energy are obtained from hard x-ray measurements of fast electron bremsstrahlung emission using a dedicated tomographic system. LHCD simulations are validated by systematic comparisons between these experimental measurements and the reconstructed signal calculated by the code R5X2 from the LUKE electron distribution. An excellent agreement is obtained in the presence of strong Landau damping (found under low density and high-power conditions in Tore Supra) for which the ray-tracing model is valid for modelling the LH wave propagation. Two aspects of the antenna spectra are found to have a significant effect on LHCD. First, the driven current is found to be proportional to the directivity, which depends upon the respective weight of the main positive and main negative lobes and is particularly sensitive to the density in front of the antenna. Second, the position of the main negative lobe in the spectrum is different for the two launchers. As this lobe drives a counter-current, the resulting driven current profile is also different for the FAM and PAM launchers.

Recent evidence for evolution of the genetic code

NASA Technical Reports Server (NTRS)

Osawa, S.; Jukes, T. H.; Watanabe, K.; Muto, A.

1992-01-01

The genetic code, formerly thought to be frozen, is now known to be in a state of evolution. This was first shown in 1979 by Barrell et al. (G. Barrell, A. T. Bankier, and J. Drouin, Nature [London] 282:189-194, 1979), who found that the universal codons AUA (isoleucine) and UGA (stop) coded for methionine and tryptophan, respectively, in human mitochondria. Subsequent studies have shown that UGA codes for tryptophan in Mycoplasma spp. and in all nonplant mitochondria that have been examined. Universal stop codons UAA and UAG code for glutamine in ciliated protozoa (except Euplotes octacarinatus) and in a green alga, Acetabularia. E. octacarinatus uses UAA for stop and UGA for cysteine. Candida species, which are yeasts, use CUG (leucine) for serine. Other departures from the universal code, all in nonplant mitochondria, are CUN (leucine) for threonine (in yeasts), AAA (lysine) for asparagine (in platyhelminths and echinoderms), UAA (stop) for tyrosine (in planaria), and AGR (arginine) for serine (in several animal orders) and for stop (in vertebrates). We propose that the changes are typically preceded by loss of a codon from all coding sequences in an organism or organelle, often as a result of directional mutation pressure, accompanied by loss of the tRNA that translates the codon. The codon reappears later by conversion of another codon and emergence of a tRNA that translates the reappeared codon with a different assignment. Changes in release factors also contribute to these revised assignments. We also discuss the use of UGA (stop) as a selenocysteine codon and the early history of the code.

Modeling the Diagnostic Criteria for Alcohol Dependence with Genetic Animal Models

PubMed Central

Kendler, Kenneth S.; Hitzemann, Robert J.

2012-01-01

A diagnosis of alcohol dependence (AD) using the DSM-IV-R is categorical, based on an individual’s manifestation of three or more symptoms from a list of seven. AD risk can be traced to both genetic and environmental sources. Most genetic studies of AD risk implicitly assume that an AD diagnosis represents a single underlying genetic factor. We recently found that the criteria for an AD diagnosis represent three somewhat distinct genetic paths to individual risk. Specifically, heavy use and tolerance versus withdrawal and continued use despite problems reflected separate genetic factors. However, some data suggest that genetic risk for AD is adequately described with a single underlying genetic risk factor. Rodent animal models for alcohol-related phenotypes typically target discrete aspects of the complex human AD diagnosis. Here, we review the literature derived from genetic animal models in an attempt to determine whether they support a single-factor or multiple-factor genetic structure. We conclude that there is modest support in the animal literature that alcohol tolerance and withdrawal reflect distinct genetic risk factors, in agreement with our human data. We suggest areas where more research could clarify this attempt to align the rodent and human data. PMID:21910077

Complete Mitochondrial Genome of Echinostoma hortense (Digenea: Echinostomatidae).

PubMed

Liu, Ze-Xuan; Zhang, Yan; Liu, Yu-Ting; Chang, Qiao-Cheng; Su, Xin; Fu, Xue; Yue, Dong-Mei; Gao, Yuan; Wang, Chun-Ren

2016-04-01

Echinostoma hortense (Digenea: Echinostomatidae) is one of the intestinal flukes with medical importance in humans. However, the mitochondrial (mt) genome of this fluke has not been known yet. The present study has determined the complete mt genome sequences of E. hortense and assessed the phylogenetic relationships with other digenean species for which the complete mt genome sequences are available in GenBank using concatenated amino acid sequences inferred from 12 protein-coding genes. The mt genome of E. hortense contained 12 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 non-coding region. The length of the mt genome of E. hortense was 14,994 bp, which was somewhat smaller than those of other trematode species. Phylogenetic analyses based on concatenated nucleotide sequence datasets for all 12 protein-coding genes using maximum parsimony (MP) method showed that E. hortense and Hypoderaeum conoideum gathered together, and they were closer to each other than to Fasciolidae and other echinostomatid trematodes. The availability of the complete mt genome sequences of E. hortense provides important genetic markers for diagnostics, population genetics, and evolutionary studies of digeneans.

Complete Mitochondrial Genome of Echinostoma hortense (Digenea: Echinostomatidae)

PubMed Central

Liu, Ze-Xuan; Zhang, Yan; Liu, Yu-Ting; Chang, Qiao-Cheng; Su, Xin; Fu, Xue; Yue, Dong-Mei; Gao, Yuan; Wang, Chun-Ren

2016-01-01

Echinostoma hortense (Digenea: Echinostomatidae) is one of the intestinal flukes with medical importance in humans. However, the mitochondrial (mt) genome of this fluke has not been known yet. The present study has determined the complete mt genome sequences of E. hortense and assessed the phylogenetic relationships with other digenean species for which the complete mt genome sequences are available in GenBank using concatenated amino acid sequences inferred from 12 protein-coding genes. The mt genome of E. hortense contained 12 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 non-coding region. The length of the mt genome of E. hortense was 14,994 bp, which was somewhat smaller than those of other trematode species. Phylogenetic analyses based on concatenated nucleotide sequence datasets for all 12 protein-coding genes using maximum parsimony (MP) method showed that E. hortense and Hypoderaeum conoideum gathered together, and they were closer to each other than to Fasciolidae and other echinostomatid trematodes. The availability of the complete mt genome sequences of E. hortense provides important genetic markers for diagnostics, population genetics, and evolutionary studies of digeneans. PMID:27180575

The optimal code searching method with an improved criterion of coded exposure for remote sensing image restoration

NASA Astrophysics Data System (ADS)

He, Lirong; Cui, Guangmang; Feng, Huajun; Xu, Zhihai; Li, Qi; Chen, Yueting

2015-03-01

Coded exposure photography makes the motion de-blurring a well-posed problem. The integration pattern of light is modulated using the method of coded exposure by opening and closing the shutter within the exposure time, changing the traditional shutter frequency spectrum into a wider frequency band in order to preserve more image information in frequency domain. The searching method of optimal code is significant for coded exposure. In this paper, an improved criterion of the optimal code searching is proposed by analyzing relationship between code length and the number of ones in the code, considering the noise effect on code selection with the affine noise model. Then the optimal code is obtained utilizing the method of genetic searching algorithm based on the proposed selection criterion. Experimental results show that the time consuming of searching optimal code decreases with the presented method. The restoration image is obtained with better subjective experience and superior objective evaluation values.

Studying the genetic basis of speciation in high gene flow marine invertebrates

PubMed Central

2016-01-01

A growing number of genes responsible for reproductive incompatibilities between species (barrier loci) exhibit the signals of positive selection. However, the possibility that genes experiencing positive selection diverge early in speciation and commonly cause reproductive incompatibilities has not been systematically investigated on a genome-wide scale. Here, I outline a research program for studying the genetic basis of speciation in broadcast spawning marine invertebrates that uses a priori genome-wide information on a large, unbiased sample of genes tested for positive selection. A targeted sequence capture approach is proposed that scores single-nucleotide polymorphisms (SNPs) in widely separated species populations at an early stage of allopatric divergence. The targeted capture of both coding and non-coding sequences enables SNPs to be characterized at known locations across the genome and at genes with known selective or neutral histories. The neutral coding and non-coding SNPs provide robust background distributions for identifying FST-outliers within genes that can, in principle, identify specific mutations experiencing diversifying selection. If natural hybridization occurs between species, the neutral coding and non-coding SNPs can provide a neutral admixture model for genomic clines analyses aimed at finding genes exhibiting strong blocks to introgression. Strongylocentrotid sea urchins are used as a model system to outline the approach but it can be used for any group that has a complete reference genome available. PMID:29491951

Pre-Service Teachers and the Re-Inscription of Whiteness: Disrupting Dominant Cultural Codes through Textual Analysis

ERIC Educational Resources Information Center

de Freitas, Elizabeth

2005-01-01

This paper draws from theorists in critical pedagogy and cultural studies in order to name and then trace the re-inscription and circulation of normative whiteness in geographically isolated rural communities. The paper examines a particular rural Canadian maritime community where my role as teacher-educator and my commitment to developing…

Tracing Ideologies of Learning in Group Talk and Their Impediments to Collaboration

ERIC Educational Resources Information Center

Anderson, Kate T.; Weninger, Csilla

2012-01-01

In this paper we examine the complex relationship between dynamics of group talk and students' ideologies of learning. Through an interactional analysis and thematic coding of group talk, this study details barriers to collaboration in a digital storytelling workshop with primary-aged youth in Singapore. Drawing on 25 h of video-recorded data, we…

Application of binomial and multinomial probability statistics to the sampling design process of a global grain tracing and recall system

USDA-ARS?s Scientific Manuscript database

Small, coded, pill-sized tracers embedded in grain are proposed as a method for grain traceability. A sampling process for a grain traceability system was designed and investigated by applying probability statistics using a science-based sampling approach to collect an adequate number of tracers fo...

Learning Uncertainty Tolerant Plans through Approximation in Complex Domains

DTIC Science & Technology

1989-01-01

Illinois BysI ~ ~Distribution/ ... AvailiblIity Codes i~Avai’l and/or I Dist I Special I U 3 ACKNOWLEDGEMENTS I 1 I would like to thank my advisor , Professor...controlling robots [Andreae84, Whitehall87]. Whitehall’s PLAND sys- tem observes a trace of robo + ztivity and develops macro-operators which include

Genetic diversity of HIV-1 non-B strains in Sicily: evidence of intersubtype recombinants by sequence analysis of gag, pol, and env genes.

PubMed

Tramuto, Fabio; Bonura, Filippa; Perna, Anna Maria; Mancuso, Salvatrice; Firenze, Alberto; Romano, Nino; Vitale, Francesco

2007-09-01

The molecular epidemiology of HIV-1 strains in Sicily (Italy) was phylogenetically investigated by the analysis of HIV-1 gag, pol, and env gene sequences from 11 HIV-1 non-B strains from 408 HIV-1-seropositive patients observed from September 2001 to August 2006. Sequences suggestive of recombination were further investigated by bootscanning analysis of various fragments. Overall, we identified several second-generation recombinant (SGRs) strains, which contained genetic material of CRF02_AG in at least one gene. Notably, three individuals were found to be infected with subsubtype A3, and one of them showed genetic recombination with subsubtype A4. The current study emphasizes the genetic analysis of gag, pol, and env genes as a powerful tool to trace the spread of complex HIV-1 recombinant forms, and highlight the genetic diversity of HIV-1 non-B strains in Italy.

The Evolution of Human Genetic Studies of Cleft Lip and Cleft Palate

PubMed Central

Marazita, Mary L.

2013-01-01

Orofacial clefts (OFCs)—primarily cleft lip and cleft palate—are among the most common birth defects in all populations worldwide, and have notable population, ethnicity, and gender differences in birth prevalence. Interest in these birth defects goes back centuries, as does formal scientific interest; scientists often used OFCs as examples or evidence during paradigm shifts in human genetics, and have also used virtually every new method of human genetic analysis to deepen our understanding of OFC. This review traces the evolution of human genetic investigations of OFC, highlights the specific insights gained about OFC through the years, and culminates in a review of recent key OFC genetic findings resulting from the powerful tools of the genomics era. Notably, OFC represents a major success for genome-wide approaches, and the field is poised for further breakthroughs in the near future. PMID:22703175

Tracing the Trans-Pacific Evolutionary History of a Domesticated Seaweed (Gracilaria chilensis) with Archaeological and Genetic Data

PubMed Central

Guillemin, Marie-Laure; Valero, Myriam; Faugeron, Sylvain; Nelson, Wendy; Destombe, Christophe

2014-01-01

The history of a domesticated marine macroalga is studied using archaeological, phylogeographic and population genetic tools. Phylogeographic and population genetic analyses demonstrated that the cultivated red alga Gracilaria chilensis colonised the Chilean coast from New Zealand. Combining archaeological observations with phylogeographic data provided evidence that exchanges between New Zealand and Chile have occurred at least before the Holocene, likely at the end of the Last Glacial Maximum (LGM) and we suggest that migration probably occurred via rafting. Furthermore, the remarkably low microsatellite diversity found in the Chilean populations compared to those in New Zealand is consistent with a recent genetic bottleneck as a result of over-exploitation of natural populations and/or the process of domestication. Therefore, the aquaculture of this seaweed, based essentially on clonal propagation, is occurring from genetically depressed populations and may be driving the species to an extinction vortex in Chile. PMID:25501717

Geometric calibration of Colour and Stereo Surface Imaging System of ESA's Trace Gas Orbiter

NASA Astrophysics Data System (ADS)

Tulyakov, Stepan; Ivanov, Anton; Thomas, Nicolas; Roloff, Victoria; Pommerol, Antoine; Cremonese, Gabriele; Weigel, Thomas; Fleuret, Francois

2018-01-01

There are many geometric calibration methods for "standard" cameras. These methods, however, cannot be used for the calibration of telescopes with large focal lengths and complex off-axis optics. Moreover, specialized calibration methods for the telescopes are scarce in literature. We describe the calibration method that we developed for the Colour and Stereo Surface Imaging System (CaSSIS) telescope, on board of the ExoMars Trace Gas Orbiter (TGO). Although our method is described in the context of CaSSIS, with camera-specific experiments, it is general and can be applied to other telescopes. We further encourage re-use of the proposed method by making our calibration code and data available on-line.

Increased apomixis expression concurrent with genetic and epigenetic variation in a newly synthesized Eragrostis curvula polyploid

NASA Astrophysics Data System (ADS)

Zappacosta, Diego C.; Ochogavía, Ana C.; Rodrigo, Juan M.; Romero, José R.; Meier, Mauro S.; Garbus, Ingrid; Pessino, Silvina C.; Echenique, Viviana C.

2014-04-01

Eragrostis curvula includes biotypes reproducing through obligate and facultative apomixis or, rarely, full sexuality. We previously generated a ``tetraploid-dihaploid-tetraploid'' series of plants consisting of a tetraploid apomictic plant (T), a sexual dihaploid plant (D) and a tetraploid artificial colchiploid (C). Initially, plant C was nearly 100% sexual. However, its capacity to form non-reduced embryo sacs dramatically increased over a four year period (2003-2007) to reach levels of 85-90%. Here, we confirmed high rates of apomixis in plant C, and used AFLPs and MSAPs to characterize the genetic and epigenetic variation observed in this plant in 2007 as compared to 2003. Of the polymorphic sequences, some had no coding potential whereas others were homologous to retrotransposons and/or protein-coding-like sequences. Our results suggest that in this particular plant system increased apomixis expression is concurrent with genetic and epigenetic modifications, possibly involving transposable elements.

Inverting the parameters of an earthquake-ruptured fault with a genetic algorithm

NASA Astrophysics Data System (ADS)

Yu, Ting-To; Fernàndez, Josè; Rundle, John B.

1998-03-01

Natural selection is the spirit of the genetic algorithm (GA): by keeping the good genes in the current generation, thereby producing better offspring during evolution. The crossover function ensures the heritage of good genes from parent to offspring. Meanwhile, the process of mutation creates a special gene, the character of which does not exist in the parent generation. A program based on genetic algorithms using C language is constructed to invert the parameters of an earthquake-ruptured fault. The verification and application of this code is shown to demonstrate its capabilities. It is determined that this code is able to find the global extreme and can be used to solve more practical problems with constraints gathered from other sources. It is shown that GA is superior to other inverting schema in many aspects. This easy handling and yet powerful algorithm should have many suitable applications in the field of geosciences.

Pitfalls of the Geographic Population Structure (GPS) Approach Applied to Human Genetic History: A Case Study of Ashkenazi Jews

PubMed Central

Flegontov, Pavel; Kassian, Alexei; Thomas, Mark G.; Fedchenko, Valentina; Changmai, Piya; Starostin, George

2016-01-01

In a recent interdisciplinary study, Das et al. have attempted to trace the homeland of Ashkenazi Jews and of their historical language, Yiddish (Das et al. 2016. Localizing Ashkenazic Jews to Primeval Villages in the Ancient Iranian Lands of Ashkenaz. Genome Biol Evol. 8:1132–1149). Das et al. applied the geographic population structure (GPS) method to autosomal genotyping data and inferred geographic coordinates of populations supposedly ancestral to Ashkenazi Jews, placing them in Eastern Turkey. They argued that this unexpected genetic result goes against the widely accepted notion of Ashkenazi origin in the Levant, and speculated that Yiddish was originally a Slavic language strongly influenced by Iranian and Turkic languages, and later remodeled completely under Germanic influence. In our view, there are major conceptual problems with both the genetic and linguistic parts of the work. We argue that GPS is a provenancing tool suited to inferring the geographic region where a modern and recently unadmixed genome is most likely to arise, but is hardly suitable for admixed populations and for tracing ancestry up to 1,000 years before present, as its authors have previously claimed. Moreover, all methods of historical linguistics concur that Yiddish is a Germanic language, with no reliable evidence for Slavic, Iranian, or Turkic substrata. PMID:27389685

The New Genealogy

ERIC Educational Resources Information Center

Roach, Ronald

2008-01-01

This article reports on developments of genealogy such as the Free African Americans Web site and the genetic ancestry tracing which point to what can be called the "new genealogy." Encouraged by the Internet's unlimited capacity as an accessible publishing space, the new genealogy has seen the unprecedented growth of genealogical research…

Efficient computation of kinship and identity coefficients on large pedigrees.

PubMed

Cheng, En; Elliott, Brendan; Ozsoyoglu, Z Meral

2009-06-01

With the rapidly expanding field of medical genetics and genetic counseling, genealogy information is becoming increasingly abundant. An important computation on pedigree data is the calculation of identity coefficients, which provide a complete description of the degree of relatedness of a pair of individuals. The areas of application of identity coefficients are numerous and diverse, from genetic counseling to disease tracking, and thus, the computation of identity coefficients merits special attention. However, the computation of identity coefficients is not done directly, but rather as the final step after computing a set of generalized kinship coefficients. In this paper, we first propose a novel Path-Counting Formula for calculating generalized kinship coefficients, which is motivated by Wright's path-counting method for computing inbreeding coefficient. We then present an efficient and scalable scheme for calculating generalized kinship coefficients on large pedigrees using NodeCodes, a special encoding scheme for expediting the evaluation of queries on pedigree graph structures. Furthermore, we propose an improved scheme using Family NodeCodes for the computation of generalized kinship coefficients, which is motivated by the significant improvement of using Family NodeCodes for inbreeding coefficient over the use of NodeCodes. We also perform experiments for evaluating the efficiency of our method, and compare it with the performance of the traditional recursive algorithm for three individuals. Experimental results demonstrate that the resulting scheme is more scalable and efficient than the traditional recursive methods for computing generalized kinship coefficients.

Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells

PubMed Central

Carlile, Thomas M.; Rojas-Duran, Maria F.; Zinshteyn, Boris; Shin, Hakyung; Bartoli, Kristen M.; Gilbert, Wendy V.

2014-01-01

Post-transcriptional modification of RNA nucleosides occurs in all living organisms. Pseudouridine, the most abundant modified nucleoside in non-coding RNAs1, enhances the function of transfer RNA and ribosomal RNA by stabilizing RNA structure2–8. mRNAs were not known to contain pseudouridine, but artificial pseudouridylation dramatically affects mRNA function – it changes the genetic code by facilitating non-canonical base pairing in the ribosome decoding center9,10. However, without evidence of naturally occurring mRNA pseudouridylation, its physiological was unclear. Here we present a comprehensive analysis of pseudouridylation in yeast and human RNAs using Pseudo-seq, a genome-wide, single-nucleotide-resolution method for pseudouridine identification. Pseudo-seq accurately identifies known modification sites as well as 100 novel sites in non-coding RNAs, and reveals hundreds of pseudouridylated sites in mRNAs. Genetic analysis allowed us to assign most of the new modification sites to one of seven conserved pseudouridine synthases, Pus1–4, 6, 7 and 9. Notably, the majority of pseudouridines in mRNA are regulated in response to environmental signals, such as nutrient deprivation in yeast and serum starvation in human cells. These results suggest a mechanism for the rapid and regulated rewiring of the genetic code through inducible mRNA modifications. Our findings reveal unanticipated roles for pseudouridylation and provide a resource for identifying the targets of pseudouridine synthases implicated in human disease11–13. PMID:25192136

Neuroscience and behavioral genetics in US criminal law: an empirical analysis

PubMed Central

Farahany, Nita A.

2016-01-01

The goal of this study was to examine the growing use of neurological and behavioral genetic evidence by criminal defendants in US criminal law. Judicial opinions issued between 2005–12 that discussed the use of neuroscience or behavioral genetics by criminal defendants were identified, coded and analysed. Criminal defendants are increasingly introducing such evidence to challenge defendants’ competency, the effectiveness of defense counsel at trial, and to mitigate punishment. PMID:27774210

Pleiotropy Analysis of Quantitative Traits at Gene Level by Multivariate Functional Linear Models

PubMed Central

Wang, Yifan; Liu, Aiyi; Mills, James L.; Boehnke, Michael; Wilson, Alexander F.; Bailey-Wilson, Joan E.; Xiong, Momiao; Wu, Colin O.; Fan, Ruzong

2015-01-01

In genetics, pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. A common approach is to analyze the phenotypic traits separately using univariate analyses and combine the test results through multiple comparisons. This approach may lead to low power. Multivariate functional linear models are developed to connect genetic variant data to multiple quantitative traits adjusting for covariates for a unified analysis. Three types of approximate F-distribution tests based on Pillai–Bartlett trace, Hotelling–Lawley trace, and Wilks’s Lambda are introduced to test for association between multiple quantitative traits and multiple genetic variants in one genetic region. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and optimal sequence kernel association test (SKAT-O). Extensive simulations were performed to evaluate the false positive rates and power performance of the proposed models and tests. We show that the approximate F-distribution tests control the type I error rates very well. Overall, simultaneous analysis of multiple traits can increase power performance compared to an individual test of each trait. The proposed methods were applied to analyze (1) four lipid traits in eight European cohorts, and (2) three biochemical traits in the Trinity Students Study. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and SKAT-O for the three biochemical traits. The approximate F-distribution tests of the proposed functional linear models are more sensitive than those of the traditional multivariate linear models that in turn are more sensitive than SKAT-O in the univariate case. The analysis of the four lipid traits and the three biochemical traits detects more association than SKAT-O in the univariate case. PMID:25809955

Pleiotropy analysis of quantitative traits at gene level by multivariate functional linear models.

PubMed

Wang, Yifan; Liu, Aiyi; Mills, James L; Boehnke, Michael; Wilson, Alexander F; Bailey-Wilson, Joan E; Xiong, Momiao; Wu, Colin O; Fan, Ruzong

2015-05-01

In genetics, pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. A common approach is to analyze the phenotypic traits separately using univariate analyses and combine the test results through multiple comparisons. This approach may lead to low power. Multivariate functional linear models are developed to connect genetic variant data to multiple quantitative traits adjusting for covariates for a unified analysis. Three types of approximate F-distribution tests based on Pillai-Bartlett trace, Hotelling-Lawley trace, and Wilks's Lambda are introduced to test for association between multiple quantitative traits and multiple genetic variants in one genetic region. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and optimal sequence kernel association test (SKAT-O). Extensive simulations were performed to evaluate the false positive rates and power performance of the proposed models and tests. We show that the approximate F-distribution tests control the type I error rates very well. Overall, simultaneous analysis of multiple traits can increase power performance compared to an individual test of each trait. The proposed methods were applied to analyze (1) four lipid traits in eight European cohorts, and (2) three biochemical traits in the Trinity Students Study. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and SKAT-O for the three biochemical traits. The approximate F-distribution tests of the proposed functional linear models are more sensitive than those of the traditional multivariate linear models that in turn are more sensitive than SKAT-O in the univariate case. The analysis of the four lipid traits and the three biochemical traits detects more association than SKAT-O in the univariate case. © 2015 WILEY PERIODICALS, INC.

Extension of the XGC code for global gyrokinetic simulations in stellarator geometry

NASA Astrophysics Data System (ADS)

Cole, Michael; Moritaka, Toseo; White, Roscoe; Hager, Robert; Ku, Seung-Hoe; Chang, Choong-Seock

2017-10-01

In this work, the total-f, gyrokinetic particle-in-cell code XGC is extended to treat stellarator geometries. Improvements to meshing tools and the code itself have enabled the first physics studies, including single particle tracing and flux surface mapping in the magnetic geometry of the heliotron LHD and quasi-isodynamic stellarator Wendelstein 7-X. These have provided the first successful test cases for our approach. XGC is uniquely placed to model the complex edge physics of stellarators. A roadmap to such a global confinement modeling capability will be presented. Single particle studies will include the physics of energetic particles' global stochastic motions and their effect on confinement. Good confinement of energetic particles is vital for a successful stellarator reactor design. These results can be compared in the core region with those of other codes, such as ORBIT3d. In subsequent work, neoclassical transport and turbulence can then be considered and compared to results from codes such as EUTERPE and GENE. After sufficient verification in the core region, XGC will move into the stellarator edge region including the material wall and neutral particle recycling.

Developing a Multi-Dimensional Hydrodynamics Code with Astrochemical Reactions

NASA Astrophysics Data System (ADS)

Kwak, Kyujin; Yang, Seungwon

2015-08-01

The Atacama Large Millimeter/submillimeter Array (ALMA) revealed high resolution molecular lines some of which are still unidentified yet. Because formation of these astrochemical molecules has been seldom studied in traditional chemistry, observations of new molecular lines drew a lot of attention from not only astronomers but also chemists both experimental and theoretical. Theoretical calculations for the formation of these astrochemical molecules have been carried out providing reaction rates for some important molecules, and some of theoretical predictions have been measured in laboratories. The reaction rates for the astronomically important molecules are now collected to form databases some of which are publically available. By utilizing these databases, we develop a multi-dimensional hydrodynamics code that includes the reaction rates of astrochemical molecules. Because this type of hydrodynamics code is able to trace the molecular formation in a non-equilibrium fashion, it is useful to study the formation history of these molecules that affects the spatial distribution of some specific molecules. We present the development procedure of this code and some test problems in order to verify and validate the developed code.

RELAP-7 Closure Correlations

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

Zou, Ling; Berry, R. A.; Martineau, R. C.

The RELAP-7 code is the next generation nuclear reactor system safety analysis code being developed at the Idaho National Laboratory (INL). The code is based on the INL’s modern scientific software development framework, MOOSE (Multi-Physics Object Oriented Simulation Environment). The overall design goal of RELAP-7 is to take advantage of the previous thirty years of advancements in computer architecture, software design, numerical integration methods, and physical models. The end result will be a reactor systems analysis capability that retains and improves upon RELAP5’s and TRACE’s capabilities and extends their analysis capabilities for all reactor system simulation scenarios. The RELAP-7 codemore » utilizes the well-posed 7-equation two-phase flow model for compressible two-phase flow. Closure models used in the TRACE code has been reviewed and selected to reflect the progress made during the past decades and provide a basis for the colure correlations implemented in the RELAP-7 code. This document provides a summary on the closure correlations that are currently implemented in the RELAP-7 code. The closure correlations include sub-grid models that describe interactions between the fluids and the flow channel, and interactions between the two phases.« less

Comparative Genomics and Identification of an Enterotoxin-Bearing Pathogenicity Island, SEPI-1/SECI-1, in Staphylococcus epidermidis Pathogenic Strains.

PubMed

Argemi, Xavier; Nanoukon, Chimène; Affolabi, Dissou; Keller, Daniel; Hansmann, Yves; Riegel, Philippe; Baba-Moussa, Lamine; Prévost, Gilles

2018-02-25

Staphylococcus epidermidis is a leading cause of nosocomial infections, majorly resistant to beta-lactam antibiotics, and may transfer several mobile genetic elements among the members of its own species, as well as to Staphylococcus aureus ; however, a genetic exchange from S. aureus to S. epidermidis remains controversial. We recently identified two pathogenic clinical strains of S. epidermidis that produce a staphylococcal enterotoxin C3-like (SEC) similar to that by S. aureus pathogenicity islands. This study aimed to determine the genetic environment of the SEC-coding sequence and to identify the mobile genetic elements. Whole-genome sequencing and annotation of the S. epidermidis strains were performed using Illumina technology and a bioinformatics pipeline for assembly, which provided evidence that the SEC-coding sequences were located in a composite pathogenicity island that was previously described in the S. epidermidis strain FRI909, called SePI-1/SeCI-1, with 83.8-89.7% nucleotide similarity. Various other plasmids were identified, particularly p_3_95 and p_4_95, which carry antibiotic resistance genes ( hsrA and dfrG , respectively), and share homologies with SAP085A and pUSA04-2-SUR11, two plasmids described in S. aureus . Eventually, one complete prophage was identified, ΦSE90, sharing 30 out of 52 coding sequences with the Acinetobacter phage vB_AbaM_IME200. Thus, the SePI-1/SeCI-1 pathogenicity island was identified in two pathogenic strains of S. epidermidis that produced a SEC enterotoxin causing septic shock. These findings suggest the existence of in vivo genetic exchange from S. aureus to S. epidermidis .

Comparative Genomics and Identification of an Enterotoxin-Bearing Pathogenicity Island, SEPI-1/SECI-1, in Staphylococcus epidermidis Pathogenic Strains

PubMed Central

Nanoukon, Chimène; Affolabi, Dissou; Keller, Daniel; Hansmann, Yves; Riegel, Philippe; Baba-Moussa, Lamine; Prévost, Gilles

2018-01-01

Staphylococcus epidermidis is a leading cause of nosocomial infections, majorly resistant to beta-lactam antibiotics, and may transfer several mobile genetic elements among the members of its own species, as well as to Staphylococcus aureus; however, a genetic exchange from S. aureus to S. epidermidis remains controversial. We recently identified two pathogenic clinical strains of S. epidermidis that produce a staphylococcal enterotoxin C3-like (SEC) similar to that by S. aureus pathogenicity islands. This study aimed to determine the genetic environment of the SEC-coding sequence and to identify the mobile genetic elements. Whole-genome sequencing and annotation of the S. epidermidis strains were performed using Illumina technology and a bioinformatics pipeline for assembly, which provided evidence that the SEC-coding sequences were located in a composite pathogenicity island that was previously described in the S. epidermidis strain FRI909, called SePI-1/SeCI-1, with 83.8–89.7% nucleotide similarity. Various other plasmids were identified, particularly p_3_95 and p_4_95, which carry antibiotic resistance genes (hsrA and dfrG, respectively), and share homologies with SAP085A and pUSA04-2-SUR11, two plasmids described in S. aureus. Eventually, one complete prophage was identified, ΦSE90, sharing 30 out of 52 coding sequences with the Acinetobacter phage vB_AbaM_IME200. Thus, the SePI-1/SeCI-1 pathogenicity island was identified in two pathogenic strains of S. epidermidis that produced a SEC enterotoxin causing septic shock. These findings suggest the existence of in vivo genetic exchange from S. aureus to S. epidermidis. PMID:29495323

A Cytogenetic Abnormality and Rare Coding Variants Identify ABCA13 as a Candidate Gene in Schizophrenia, Bipolar Disorder, and Depression

PubMed Central

Knight, Helen M.; Pickard, Benjamin S.; Maclean, Alan; Malloy, Mary P.; Soares, Dinesh C.; McRae, Allan F.; Condie, Alison; White, Angela; Hawkins, William; McGhee, Kevin; van Beck, Margaret; MacIntyre, Donald J.; Starr, John M.; Deary, Ian J.; Visscher, Peter M.; Porteous, David J.; Cannon, Ronald E.; St Clair, David; Muir, Walter J.; Blackwood, Douglas H.R.

2009-01-01

Schizophrenia and bipolar disorder are leading causes of morbidity across all populations, with heritability estimates of ∼80% indicating a substantial genetic component. Population genetics and genome-wide association studies suggest an overlap of genetic risk factors between these illnesses but it is unclear how this genetic component is divided between common gene polymorphisms, rare genomic copy number variants, and rare gene sequence mutations. We report evidence that the lipid transporter gene ABCA13 is a susceptibility factor for both schizophrenia and bipolar disorder. After the initial discovery of its disruption by a chromosome abnormality in a person with schizophrenia, we resequenced ABCA13 exons in 100 cases with schizophrenia and 100 controls. Multiple rare coding variants were identified including one nonsense and nine missense mutations and compound heterozygosity/homozygosity in six cases. Variants were genotyped in additional schizophrenia, bipolar, depression (n > 1600), and control (n > 950) cohorts and the frequency of all rare variants combined was greater than controls in schizophrenia (OR = 1.93, p = 0.0057) and bipolar disorder (OR = 2.71, p = 0.00007). The population attributable risk of these mutations was 2.2% for schizophrenia and 4.0% for bipolar disorder. In a study of 21 families of mutation carriers, we genotyped affected and unaffected relatives and found significant linkage (LOD = 4.3) of rare variants with a phenotype including schizophrenia, bipolar disorder, and major depression. These data identify a candidate gene, highlight the genetic overlap between schizophrenia, bipolar disorder, and depression, and suggest that rare coding variants may contribute significantly to risk of these disorders. PMID:19944402

Allele-Selective Transcriptome Recruitment to Polysomes Primed for Translation: Protein-Coding and Noncoding RNAs, and RNA Isoforms.

PubMed

Mascarenhas, Roshan; Pietrzak, Maciej; Smith, Ryan M; Webb, Amy; Wang, Danxin; Papp, Audrey C; Pinsonneault, Julia K; Seweryn, Michal; Rempala, Grzegorz; Sadee, Wolfgang

2015-01-01

mRNA translation into proteins is highly regulated, but the role of mRNA isoforms, noncoding RNAs (ncRNAs), and genetic variants remains poorly understood. mRNA levels on polysomes have been shown to correlate well with expressed protein levels, pointing to polysomal loading as a critical factor. To study regulation and genetic factors of protein translation we measured levels and allelic ratios of mRNAs and ncRNAs (including microRNAs) in lymphoblast cell lines (LCL) and in polysomal fractions. We first used targeted assays to measure polysomal loading of mRNA alleles, confirming reported genetic effects on translation of OPRM1 and NAT1, and detecting no effect of rs1045642 (3435C>T) in ABCB1 (MDR1) on polysomal loading while supporting previous results showing increased mRNA turnover of the 3435T allele. Use of high-throughput sequencing of complete transcript profiles (RNA-Seq) in three LCLs revealed significant differences in polysomal loading of individual RNA classes and isoforms. Correlated polysomal distribution between protein-coding and non-coding RNAs suggests interactions between them. Allele-selective polysome recruitment revealed strong genetic influence for multiple RNAs, attributable either to differential expression of RNA isoforms or to differential loading onto polysomes, the latter defining a direct genetic effect on translation. Genes identified by different allelic RNA ratios between cytosol and polysomes were enriched with published expression quantitative trait loci (eQTLs) affecting RNA functions, and associations with clinical phenotypes. Polysomal RNA-Seq combined with allelic ratio analysis provides a powerful approach to study polysomal RNA recruitment and regulatory variants affecting protein translation.

Three-Dimensional Algebraic Models of the tRNA Code and 12 Graphs for Representing the Amino Acids.

PubMed

José, Marco V; Morgado, Eberto R; Guimarães, Romeu Cardoso; Zamudio, Gabriel S; de Farías, Sávio Torres; Bobadilla, Juan R; Sosa, Daniela

2014-08-11

Three-dimensional algebraic models, also called Genetic Hotels, are developed to represent the Standard Genetic Code, the Standard tRNA Code (S-tRNA-C), and the Human tRNA code (H-tRNA-C). New algebraic concepts are introduced to be able to describe these models, to wit, the generalization of the 2n-Klein Group and the concept of a subgroup coset with a tail. We found that the H-tRNA-C displayed broken symmetries in regard to the S-tRNA-C, which is highly symmetric. We also show that there are only 12 ways to represent each of the corresponding phenotypic graphs of amino acids. The averages of statistical centrality measures of the 12 graphs for each of the three codes are carried out and they are statistically compared. The phenotypic graphs of the S-tRNA-C display a common triangular prism of amino acids in 10 out of the 12 graphs, whilst the corresponding graphs for the H-tRNA-C display only two triangular prisms. The graphs exhibit disjoint clusters of amino acids when their polar requirement values are used. We contend that the S-tRNA-C is in a frozen-like state, whereas the H-tRNA-C may be in an evolving state.

7 CFR 457.112 - Hybrid sorghum seed crop insurance provisions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... produced by crossing a male and female parent plant, each having a different genetic character. This... formula for establishing the value must be based on data provided by a public third party that establishes..., number or code assigned to a specific genetic cross by the seed company or the Special Provisions for the...

Two Aspects of Meaningful Problem Solving in Science.

ERIC Educational Resources Information Center

Stewart, James

1982-01-01

Presents a model for solving genetics problems when problem statements include information on which alleles are dominant/recessive and on what forms of a trait are coded for by the alleles. Includes procedural steps employed in a solution and conceptual knowledge of genetics/meiosis allowing students to justify what they have done. (Author/JN)

DNA as information: at the crossroads between biology, mathematics, physics and chemistry

PubMed Central

2016-01-01

On the one hand, biology, chemistry and also physics tell us how the process of translating the genetic information into life could possibly work, but we are still very far from a complete understanding of this process. On the other hand, mathematics and statistics give us methods to describe such natural systems—or parts of them—within a theoretical framework. Also, they provide us with hints and predictions that can be tested at the experimental level. Furthermore, there are peculiar aspects of the management of genetic information that are intimately related to information theory and communication theory. This theme issue is aimed at fostering the discussion on the problem of genetic coding and information through the presentation of different innovative points of view. The aim of the editors is to stimulate discussions and scientific exchange that will lead to new research on why and how life can exist from the point of view of the coding and decoding of genetic information. The present introduction represents the point of view of the editors on the main aspects that could be the subject of future scientific debate. PMID:26857674

Biological Information Transfer Beyond the Genetic Code: The Sugar Code

NASA Astrophysics Data System (ADS)

Gabius, H.-J.

In the era of genetic engineering, cloning, and genome sequencing the focus of research on the genetic code has received an even further accentuation in the public eye. In attempting, however, to understand intra- and intercellular recognition processes comprehensively, the two biochemical dimensions established by nucleic acids and proteins are not sufficient to satisfactorily explain all molecular events in, for example, cell adhesion or routing. The consideration of further code systems is essential to bridge this gap. A third biochemical alphabet forming code words with an information storage capacity second to no other substance class in rather small units (words, sentences) is established by monosaccharides (letters). As hardware oligosaccharides surpass peptides by more than seven orders of magnitude in the theoretical ability to build isomers, when the total of conceivable hexamers is calculated. In addition to the sequence complexity, the use of magnetic resonance spectroscopy and molecular modeling has been instrumental in discovering that even small glycans can often reside in not only one but several distinct low-energy conformations (keys). Intriguingly, conformers can display notably different capacities to fit snugly into the binding site of nonhomologous receptors (locks). This process, experimentally verified for two classes of lectins, is termed "differential conformer selection." It adds potential for shifts of the conformer equilibrium to modulate ligand properties dynamically and reversibly to the well-known changes in sequence (including anomeric positioning and linkage points) and in pattern of substitution, for example, by sulfation. In the intimate interplay with sugar receptors (lectins, enzymes, and antibodies) the message of coding units of the sugar code is deciphered. Their recognition will trigger postbinding signaling and the intended biological response. Knowledge about the driving forces for the molecular rendezvous, i.e., contributions of bidentate or cooperative hydrogen bonds, dispersion forces, stacking, and solvent rearrangement, will enable the design of high-affinity ligands or mimetics thereof. They embody clinical applications reaching from receptor localization in diagnostic pathology to cell type-selective targeting of drugs and inhibition of undesired cell adhesion in bacterial/viral infections, inflammation, or metastasis.

Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture

PubMed Central

Zheng, Hou-Feng; Forgetta, Vincenzo; Hsu, Yi-Hsiang; Estrada, Karol; Rosello-Diez, Alberto; Leo, Paul J; Dahia, Chitra L; Park-Min, Kyung Hyun; Tobias, Jonathan H; Kooperberg, Charles; Kleinman, Aaron; Styrkarsdottir, Unnur; Liu, Ching-Ti; Uggla, Charlotta; Evans, Daniel S; Nielson, Carrie M; Walter, Klaudia; Pettersson-Kymmer, Ulrika; McCarthy, Shane; Eriksson, Joel; Kwan, Tony; Jhamai, Mila; Trajanoska, Katerina; Memari, Yasin; Min, Josine; Huang, Jie; Danecek, Petr; Wilmot, Beth; Li, Rui; Chou, Wen-Chi; Mokry, Lauren E; Moayyeri, Alireza; Claussnitzer, Melina; Cheng, Chia-Ho; Cheung, Warren; Medina-Gómez, Carolina; Ge, Bing; Chen, Shu-Huang; Choi, Kwangbom; Oei, Ling; Fraser, James; Kraaij, Robert; Hibbs, Matthew A; Gregson, Celia L; Paquette, Denis; Hofman, Albert; Wibom, Carl; Tranah, Gregory J; Marshall, Mhairi; Gardiner, Brooke B; Cremin, Katie; Auer, Paul; Hsu, Li; Ring, Sue; Tung, Joyce Y; Thorleifsson, Gudmar; Enneman, Anke W; van Schoor, Natasja M; de Groot, Lisette C.P.G.M.; van der Velde, Nathalie; Melin, Beatrice; Kemp, John P; Christiansen, Claus; Sayers, Adrian; Zhou, Yanhua; Calderari, Sophie; van Rooij, Jeroen; Carlson, Chris; Peters, Ulrike; Berlivet, Soizik; Dostie, Josée; Uitterlinden, Andre G; Williams, Stephen R.; Farber, Charles; Grinberg, Daniel; LaCroix, Andrea Z; Haessler, Jeff; Chasman, Daniel I; Giulianini, Franco; Rose, Lynda M; Ridker, Paul M; Eisman, John A; Nguyen, Tuan V; Center, Jacqueline R; Nogues, Xavier; Garcia-Giralt, Natalia; Launer, Lenore L; Gudnason, Vilmunder; Mellström, Dan; Vandenput, Liesbeth; Karlsson, Magnus K; Ljunggren, Östen; Svensson, Olle; Hallmans, Göran; Rousseau, François; Giroux, Sylvie; Bussière, Johanne; Arp, Pascal P; Koromani, Fjorda; Prince, Richard L; Lewis, Joshua R; Langdahl, Bente L; Hermann, A Pernille; Jensen, Jens-Erik B; Kaptoge, Stephen; Khaw, Kay-Tee; Reeve, Jonathan; Formosa, Melissa M; Xuereb-Anastasi, Angela; Åkesson, Kristina; McGuigan, Fiona E; Garg, Gaurav; Olmos, Jose M; Zarrabeitia, Maria T; Riancho, Jose A; Ralston, Stuart H; Alonso, Nerea; Jiang, Xi; Goltzman, David; Pastinen, Tomi; Grundberg, Elin; Gauguier, Dominique; Orwoll, Eric S; Karasik, David; Davey-Smith, George; Smith, Albert V; Siggeirsdottir, Kristin; Harris, Tamara B; Zillikens, M Carola; van Meurs, Joyce BJ; Thorsteinsdottir, Unnur; Maurano, Matthew T; Timpson, Nicholas J; Soranzo, Nicole; Durbin, Richard; Wilson, Scott G; Ntzani, Evangelia E; Brown, Matthew A; Stefansson, Kari; Hinds, David A; Spector, Tim; Cupples, L Adrienne; Ohlsson, Claes; Greenwood, Celia MT; Jackson, Rebecca D; Rowe, David W; Loomis, Cynthia A; Evans, David M; Ackert-Bicknell, Cheryl L; Joyner, Alexandra L; Duncan, Emma L; Kiel, Douglas P; Rivadeneira, Fernando; Richards, J Brent

2016-01-01

SUMMARY The extent to which low-frequency (minor allele frequency [MAF] between 1–5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is largely unknown. Bone mineral density (BMD) is highly heritable, is a major predictor of osteoporotic fractures and has been previously associated with common genetic variants1–8, and rare, population-specific, coding variants9. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n=2,882 from UK10K), whole-exome sequencing (n= 3,549), deep imputation of genotyped samples using a combined UK10K/1000Genomes reference panel (n=26,534), and de-novo replication genotyping (n= 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size 4-fold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564[T], MAF = 1.7%, replication effect size = +0.20 standard deviations [SD], Pmeta = 2×10−14), which was also associated with a decreased risk of fracture (OR = 0.85; P = 2×10−11; ncases = 98,742 and ncontrols = 409,511). Using an En1Cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, likely as a consequence of high bone turn-over. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817[T], MAF = 1.1%, replication effect size = +0.39 SD, Pmeta = 1×10−11). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population. PMID:26367794

Co-occurrence profiles of trace elements in potable water systems: a case study.

PubMed

Andra, Syam S; Makris, Konstantinos C; Charisiadis, Pantelis; Costa, Costas N

2014-11-01

Potable water samples (N = 74) from 19 zip code locations in a region of Greece were profiled for 13 trace elements composition using inductively coupled plasma mass spectrometry. The primary objective was to monitor the drinking water quality, while the primary focus was to find novel associations in trace elements occurrence that may further shed light on common links in their occurrence and fate in the pipe scales and corrosion products observed in urban drinking water distribution systems. Except for arsenic at two locations and in six samples, rest of the analyzed elements was below maximum contaminant levels, for which regulatory values are available. Further, we attempted to hierarchically cluster trace elements based on their covariances resulting in two groups; one with arsenic, antimony, zinc, cadmium, and copper and the second with the rest of the elements. The grouping trends were partially explained by elements' similar chemical activities in water, underscoring their potential for co-accumulation and co-mobilization phenomena from pipe scales into finished water. Profiling patterns of trace elements in finished water could be indicative of their load on pipe scales and corrosion products, with a corresponding risk of episodic contaminant release. Speculation was made on the role of disinfectants and disinfection byproducts in mobilizing chemically similar trace elements of human health interest from pipe scales to tap water. It is warranted that further studies may eventually prove useful to water regulators from incorporating the acquired knowledge in the drinking water safety plans.

Numerical Simulation of Single-anode and Double-anode Magnetron Injection Guns for 127.5 GHz 1 MW Gyrotron

NASA Astrophysics Data System (ADS)

Singh, Udaybir; Kumar, Nitin; Kumar, Anil; Purohit, Laxmi Prasad; Sinha, Ashok Kumar

2011-07-01

This paper presents the design of two types of magnetron injection guns (MIG's) for 1 MW, 127.5 GHz gyrotron. TE24,8 mode has been chosen as the operating mode. In-house developed code MIGSYN has been used to estimate the initial gun parameters. The electron trajectory tracing program EGUN and in-house developed code MIGANS have been used to optimize the single-anode and the double-anode design for 80 kV, 40 A MIG. The parametric analysis of MIG has also been presented. The advantages and the disadvantages of each kind of configuration have been critically examined.

Genetic diversity in Monoporeia affinis at polluted and reference sites of the Baltic Bothnian Bay.

PubMed

Guban, Peter; Wennerström, Lovisa; Elfwing, Tina; Sundelin, Brita; Laikre, Linda

2015-04-15

The amphipod Monoporeia affinis plays an important role in the Baltic Sea ecosystem as prey and as detritivore. The species is monitored for contaminant effects, but almost nothing is known about its genetics in this region. A pilot screening for genetic variation at the mitochondrial COI gene was performed in 113 individuals collected at six sites in the northern Baltic. Three coastal sites were polluted by pulp mill effluents, PAHs, and trace metals, and two coastal reference sites were without obvious connection to pollution sources. An off-coastal reference site was also included. Contaminated sites showed lower levels of genetic diversity than the coastal reference ones although the difference was not statistically significant. Divergence patterns measured as ΦST showed no significant differentiation within reference and polluted groups, but there was significant genetic divergence between them. The off-coastal sample differed significantly from all coastal sites and also showed lower genetic variation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Most Used Codons per Amino Acid and per Genome in the Code of Man Compared to Other Organisms According to the Rotating Circular Genetic Code

PubMed Central

Castro-Chavez, Fernando

2011-01-01

My previous theoretical research shows that the rotating circular genetic code is a viable tool to make easier to distinguish the rules of variation applied to the amino acid exchange; it presents a precise and positional bio-mathematical balance of codons, according to the amino acids they codify. Here, I demonstrate that when using the conventional or classic circular genetic code, a clearer pattern for the human codon usage per amino acid and per genome emerges. The most used human codons per amino acid were the ones ending with the three hydrogen bond nucleotides: C for 12 amino acids and G for the remaining 8, plus one codon for arginine ending in A that was used approximately with the same frequency than the one ending in G for this same amino acid (plus *). The most used codons in man fall almost all the time at the rightmost position, clockwise, ending either in C or in G within the circular genetic code. The human codon usage per genome is compared to other organisms such as fruit flies (Drosophila melanogaster), squid (Loligo pealei), and many others. The biosemiotic codon usage of each genomic population or ‘Theme’ is equated to a ‘molecular language’. The C/U choice or difference, and the G/A difference in the third nucleotide of the most used codons per amino acid are illustrated by comparing the most used codons per genome in humans and squids. The human distribution in the third position of most used codons is a 12-8-2, C-G-A, nucleotide ending signature, while the squid distribution in the third position of most used codons was an odd, or uneven, distribution in the third position of its most used codons: 13-6-3, U-A-G, as its nucleotide ending signature. These findings may help to design computational tools to compare human genomes, to determine the exchangeability between compatible codons and amino acids, and for the early detection of incompatible changes leading to hereditary diseases. PMID:22997484

Observation of temperature trace, induced by changing of temperature inside the human body, on the human body skin using commercially available IR camera

NASA Astrophysics Data System (ADS)

Trofimov, Vyacheslav A.; Trofimov, Vladislav V.

2015-05-01

As it is well-known, application of the passive THz camera for the security problems is very promising way. It allows seeing concealed object without contact with a person and this camera is non-dangerous for a person. In previous papers, we demonstrate new possibility of the passive THz camera using for a temperature difference observing on the human skin if this difference is caused by different temperatures inside the body. For proof of validity of our statement we make the similar physical experiment using the IR camera. We show a possibility of temperature trace on human body skin, caused by changing of temperature inside the human body due to water drinking. We use as a computer code that is available for treatment of images captured by commercially available IR camera, manufactured by Flir Corp., as well as our developed computer code for computer processing of these images. Using both codes we demonstrate clearly changing of human body skin temperature induced by water drinking. Shown phenomena are very important for the detection of forbidden samples and substances concealed inside the human body using non-destructive control without X-rays using. Early we have demonstrated such possibility using THz radiation. Carried out experiments can be used for counter-terrorism problem solving. We developed original filters for computer processing of images captured by IR cameras. Their applications for computer processing of images results in a temperature resolution enhancing of cameras.

Archive of Digital Chirp Subbottom Profile Data Collected During USGS Cruise 14BIM05 Offshore of Breton Island, Louisiana, August 2014

USGS Publications Warehouse

Forde, Arnell S.; Flocks, James G.; Wiese, Dana S.; Fredericks, Jake J.

2016-03-29

The archived trace data are in standard SEG Y rev. 0 format (Barry and others, 1975); the first 3,200 bytes of the card image header are in American Standard Code for Information Interchange (ASCII) format instead of Extended Binary Coded Decimal Interchange Code (EBCDIC) format. The SEG Y files are available on the DVD version of this report or online, downloadable via the USGS Coastal and Marine Geoscience Data System (http://cmgds.marine.usgs.gov). The data are also available for viewing using GeoMapApp (http://www.geomapapp.org) and Virtual Ocean (http://www.virtualocean.org) multi-platform open source software. The Web version of this archive does not contain the SEG Y trace files. To obtain the complete DVD archive, contact USGS Information Services at 1-888-ASK-USGS or infoservices@usgs.gov. The SEG Y files may be downloaded and processed with commercial or public domain software such as Seismic Unix (SU) (Cohen and Stockwell, 2010). See the How To Download SEG Y Data page for download instructions. The printable profiles are provided as Graphics Interchange Format (GIF) images processed and gained using SU software and can be viewed from theProfiles page or by using the links located on the trackline maps; refer to the Software page for links to example SU processing scripts.

Magnetic chaos healing in the helical reversed-field pinch: indications from the volume-preserving field line tracing code NEMATO

NASA Astrophysics Data System (ADS)

Bonfiglio, D.; Veranda, M.; Cappello, S.; Chacón, L.; Spizzo, G.

2010-11-01

The emergence of a self-organized reversed-field pinch (RFP) helical regime, first shown by 3D MHD numerical simulations, has been highlighted in the RFX-mod experiment at high current operation (IP above 1 MA). In fact, a quasi-stationary helical configuration spontaneously appears, characterized by strong internal electron transport barriers. In such regime electron temperature and density become, to a very good approximation, functions of the helical flux coordinate related to the dominant helical magnetic component. In addition, this regime is diagnosed to be associated with the topological transition to a single-helical-axis (SHAx) state, achieved after the expulsion of the separatrix of the dominant mode's magnetic island. The SHAx state is theoretically predicted to be resilient to the magnetic chaos induced by secondary modes. In this paper, we present initial results of the volume-preserving field line tracing code NEMATO [Finn J M and Chacón L 2005 Phys. Plasmas 12 054503] applied to study the magnetic topology resulting from 3D MHD simulations of the RFP. First, a successful 2D verification test of the code is shown, then, initial application to a systematic study of chaos healing in the helical RFP is discussed. The separatrix disappearance is confirmed to play an essential role for chaos healing. The triggering effect of a reversed magnetic shear for the formation of ordered surfaces within magnetic chaos is also diagnosed.

Magnetic chaos healing in hte helical reversed-field pinch: indications from the volume-preserving field line tracing code NEMATO

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

Bonfiglio, Daniele; Veranda, M.; Cappello, Susanna

2010-01-01

The emergence of a self-organized reversed-field pinch (RFP) helical regime, first shown by 3D MHD numerical simulations, has been highlighted in the RFX-mod experiment at high current operation (IP above 1 MA). In fact, a quasi-stationary helical configuration spontaneously appears, characterized by strong internal electron transport barriers. In such regime electron temperature and density become, to a very good approximation, functions of the helical flux coordinate related to the dominant helical magnetic component. In addition, this regime is diagnosed to be associated with the topological transition to a single-helical-axis (SHAx) state, achieved after the expulsion of the separatrix of themore » dominant mode's magnetic island. The SHAx state is theoretically predicted to be resilient to the magnetic chaos induced by secondary modes. In this paper, we present initial results of the volume-preserving field line tracing code nemato [Finn J M and Chacon L 2005 Phys. Plasmas 12 054503] applied to study the magnetic topology resulting from 3D MHD simulations of the RFP. First, a successful 2D verification test of the code is shown, then, initial application to a systematic study of chaos healing in the helical RFP is discussed. The separatrix disappearance is confirmed to play an essential role for chaos healing. The triggering effect of a reversed magnetic shear for the formation of ordered surfaces within magnetic chaos is also diagnosed.« less

WOLF: a computer code package for the calculation of ion beam trajectories

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

Vogel, D.L.

1985-10-01

The WOLF code solves POISSON'S equation within a user-defined problem boundary of arbitrary shape. The code is compatible with ANSI FORTRAN and uses a two-dimensional Cartesian coordinate geometry represented on a triangular lattice. The vacuum electric fields and equipotential lines are calculated for the input problem. The use may then introduce a series of emitters from which particles of different charge-to-mass ratios and initial energies can originate. These non-relativistic particles will then be traced by WOLF through the user-defined region. Effects of ion and electron space charge are included in the calculation. A subprogram PISA forms part of this codemore » and enables optimization of various aspects of the problem. The WOLF package also allows detailed graphics analysis of the computed results to be performed.« less

Genetic diversity-seeing the forest through the trees

Treesearch

M. Thompson Conkle

1992-01-01

Forest trees, populations, races, species, and taxonomic groups above the species level display rich variation in biochemical markers. The variation stems from inherited modifications that trace back in time, through converging ancestries, towards common progenitors. Past movements of continents, mountain building events, and climate changes isolated forest populations...

Two-Generation Programs and Health

ERIC Educational Resources Information Center

Glied, Sherry; Oellerich, Don

2014-01-01

Parents' health and children's health are closely intertwined--healthier parents have healthier children, and vice versa. Genetics accounts for some of this relationship, but much of it can be traced to environment and behavior, and the environmental and behavioral risk factors for poor health disproportionately affect families living in…

Global population genomics and comparisons of selective signatures from two invasions of melon fly, Zeugodacus cucurbitae (Diptera: Tephritidae)

USDA-ARS?s Scientific Manuscript database

Population genetics is a powerful tool for invasion biology and pest management, from tracing invasion pathways to informing management decisions with inference of population demographics. Genomics greatly increases the resolution of population-scale analyses, yet outside of model species with exten...

Viruses as groundwater tracers: using ecohydrology to characterize short travel times in aquifers

USDA-ARS?s Scientific Manuscript database

Viruses are attractive tracers of short (<3 yr) travel times in aquifers because they have unique genetic signatures, are detectable in trace quantities, and are mobile and stable in groundwater. Virus “snaphots” result from infection and disappearance over time as a community develops resistance. T...

Exploring Agricultural and Biotechnical Engineering through Hands-On Integrated STEM

ERIC Educational Resources Information Center

Preble, Brian C.

2015-01-01

The manipulation of the natural world in the form of plant materials to design, control, and grow desirable agricultural commodities was central to the establishment and advancement of civilization. Modern developments in genetically modified organisms (GMOs or biologically engineered foods) can trace their origins to macro practices developed and…

Global Coordinates and Exact Aberration Calculations Applied to Physical Optics Modeling of Complex Optical Systems

NASA Astrophysics Data System (ADS)

Lawrence, G.; Barnard, C.; Viswanathan, V.

1986-11-01

Historically, wave optics computer codes have been paraxial in nature. Folded systems could be modeled by "unfolding" the optical system. Calculation of optical aberrations is, in general, left for the analyst to do with off-line codes. While such paraxial codes were adequate for the simpler systems being studied 10 years ago, current problems such as phased arrays, ring resonators, coupled resonators, and grazing incidence optics require a major advance in analytical capability. This paper describes extension of the physical optics codes GLAD and GLAD V to include a global coordinate system and exact ray aberration calculations. The global coordinate system allows components to be positioned and rotated arbitrarily. Exact aberrations are calculated for components in aligned or misaligned configurations by using ray tracing to compute optical path differences and diffraction propagation. Optical path lengths between components and beam rotations in complex mirror systems are calculated accurately so that coherent interactions in phased arrays and coupled devices may be treated correctly.

Applications of automatic differentiation in computational fluid dynamics

NASA Technical Reports Server (NTRS)

Green, Lawrence L.; Carle, A.; Bischof, C.; Haigler, Kara J.; Newman, Perry A.

1994-01-01

Automatic differentiation (AD) is a powerful computational method that provides for computing exact sensitivity derivatives (SD) from existing computer programs for multidisciplinary design optimization (MDO) or in sensitivity analysis. A pre-compiler AD tool for FORTRAN programs called ADIFOR has been developed. The ADIFOR tool has been easily and quickly applied by NASA Langley researchers to assess the feasibility and computational impact of AD in MDO with several different FORTRAN programs. These include a state-of-the-art three dimensional multigrid Navier-Stokes flow solver for wings or aircraft configurations in transonic turbulent flow. With ADIFOR the user specifies sets of independent and dependent variables with an existing computer code. ADIFOR then traces the dependency path throughout the code, applies the chain rule to formulate derivative expressions, and generates new code to compute the required SD matrix. The resulting codes have been verified to compute exact non-geometric and geometric SD for a variety of cases. in less time than is required to compute the SD matrix using centered divided differences.

Stability or stasis in the names of organisms: the evolving codes of nomenclature.

PubMed Central

Knapp, Sandra; Lamas, Gerardo; Lughadha, Eimear Nic; Novarino, Gianfranco

2004-01-01

Nomenclature, far from being a dry dusty subject, is today more relevant than ever before. Researchers into genomics are discovering again the need for systems of nomenclature-names are what we use to communicate about organisms, and by extension the rest of their biology. Here, we briefly outline the history of the published international codes of nomenclature, tracing them from the time of Linnaeus in the eighteenth century to the present day. We then outline some of what we feel are the major challenges that face the codes in the twenty-first century; focusing primarily on publication, priority, typification and the role of science in the naming of organisms. We conclude that the codes are essential for taxonomists in the pursuance of their science, and that the democratic nature of decision-making in the regulation of the rules of nomenclature, though sometimes perceived as a potential weakness, is in fact one of its great strengths. PMID:15253348

Characteristic Evolution and Matching

NASA Astrophysics Data System (ADS)

Winicour, Jeffrey

2012-01-01

I review the development of numerical evolution codes for general relativity based upon the characteristic initial-value problem. Progress in characteristic evolution is traced from the early stage of 1D feasibility studies to 2D-axisymmetric codes that accurately simulate the oscillations and gravitational collapse of relativistic stars and to current 3D codes that provide pieces of a binary black-hole spacetime. Cauchy codes have now been successful at simulating all aspects of the binary black-hole problem inside an artificially constructed outer boundary. A prime application of characteristic evolution is to extend such simulations to null infinity where the waveform from the binary inspiral and merger can be unambiguously computed. This has now been accomplished by Cauchy-characteristic extraction, where data for the characteristic evolution is supplied by Cauchy data on an extraction worldtube inside the artificial outer boundary. The ultimate application of characteristic evolution is to eliminate the role of this outer boundary by constructing a global solution via Cauchy-characteristic matching. Progress in this direction is discussed.

The minimal autopoietic unit.

PubMed

Luisi, Pier Luigi

2014-12-01

It is argued that closed, cell-like compartments, may have existed in prebiotic time, showing a simplified metabolism which was bringing about a primitive form of stationary state- a kind of homeostasis. The autopoietic primitive cell can be taken as an example and there are preliminary experimental data supporting the possible existence of this primitive form of cell activity. The genetic code permits, among other things, the continuous self-reproduction of proteins; enzymic proteins permit the synthesis of nucleic acids, and in this way there is a perfect recycling between the two most important classes of biopolymers in our life. On the other hand, the genetic code is a complex machinery, which cannot be posed at the very early time of the origin of life. And the question then arises, whether some form of alternative beginning, prior to the genetic code, would have been possible: and this is the core of the question asked. Is something with the flavor of early life conceivable, prior to the genetic code? My answer is positive, although I am too well aware that the term "conceivable" does not mean that this something is easily to be performed experimentally. To illustrate my answer, I would first go back to the operational description of cellular life as given by the theory of autopoiesis. Accordingly, a living cell is an open system capable of self-maintenance, due to a process of internal self-regeneration of the components, all within a boundary which is itself product from within. This is a universal code, valid not only for a cell, but for any living macroscopic entity, as no living system exists on Earth which does not obey this principle. In this definition (or better operational description) there is no mention of DNA or genetic code. I added in that definition the term "open system"-which is not present in the primary literature (Varela, et al., 1974) to make clear that every living system is indeed an open system-without this addition, it may seem that with autopoiesis we are dealing with a perpetuum mobile, against the second principle of thermodynamics. Now consider the following figure (Fig. 1). It represents in a very schematic form a cell, as an open system, with a semipermeable membrane constituted by the chemical S, which permits the entrance of the nutrient A and the elimination of the decay product P. A is transformed inside the cell into S by a chemical reaction characterized by kgen, and S can be transformed into P by the reaction kdec. The two reactions actually may represent two entire families of reaction, in the sense that one can envisage several A and several S and several P.

Molecular characterization of serotype Asia-1 foot-and-mouth disease viruses in Pakistan and Afghanistan; emergence of a new genetic Group and evidence for a novel recombinant virus.

PubMed

Jamal, Syed M; Ferrari, Giancarlo; Ahmed, Safia; Normann, Preben; Belsham, Graham J

2011-12-01

Foot-and-mouth disease (FMD) is endemic in Pakistan and Afghanistan. The FMD virus serotypes O, A and Asia-1 are responsible for the outbreaks in these countries. Diverse strains of FMDV, even within the same serotype, co-circulate. Characterization of the viruses in circulation can facilitate appropriate vaccine selection and tracing of outbreaks. The present study characterized foot-and-mouth disease serotype Asia-1 viruses circulating in Pakistan and Afghanistan during the period 1998-2009. Phylogenetic analysis of FMDV type Asia-1 revealed that three different genetic Groups of serotype Asia-1 have circulated in Pakistan during this time. These are Group-II, -VI and, recently, a novel Group (designated here as Group-VII). This new Group has not been detected in neighbouring Afghanistan during the study period but viruses from Groups I and -II are in circulation there. Using near complete genome sequences, from FMD viruses of serotypes Asia-1 and A that are currently circulating in Pakistan, we have identified an interserotypic recombinant virus, which has the VP2-VP3-VP1-2A coding sequences derived from a Group-VII Asia-1 virus and the remainder of the genome from a serotype A virus of the A-Iran05(AFG-07) sub-lineage. The Asia-1 FMDVs currently circulating in Pakistan and Afghanistan are not efficiently neutralized by antisera raised against the Asia-1/Shamir vaccine strain. Thus, new Asia-1 vaccine strains may be required to block the spread of the current Asia-1 viruses. Copyright © 2011 Elsevier B.V. All rights reserved.

GenInfoGuard--a robust and distortion-free watermarking technique for genetic data.

PubMed

Iftikhar, Saman; Khan, Sharifullah; Anwar, Zahid; Kamran, Muhammad

2015-01-01

Genetic data, in digital format, is used in different biological phenomena such as DNA translation, mRNA transcription and protein synthesis. The accuracy of these biological phenomena depend on genetic codes and all subsequent processes. To computerize the biological procedures, different domain experts are provided with the authorized access of the genetic codes; as a consequence, the ownership protection of such data is inevitable. For this purpose, watermarks serve as the proof of ownership of data. While protecting data, embedded hidden messages (watermarks) influence the genetic data; therefore, the accurate execution of the relevant processes and the overall result becomes questionable. Most of the DNA based watermarking techniques modify the genetic data and are therefore vulnerable to information loss. Distortion-free techniques make sure that no modifications occur during watermarking; however, they are fragile to malicious attacks and therefore cannot be used for ownership protection (particularly, in presence of a threat model). Therefore, there is a need for a technique that must be robust and should also prevent unwanted modifications. In this spirit, a watermarking technique with aforementioned characteristics has been proposed in this paper. The proposed technique makes sure that: (i) the ownership rights are protected by means of a robust watermark; and (ii) the integrity of genetic data is preserved. The proposed technique-GenInfoGuard-ensures its robustness through the "watermark encoding" in permuted values, and exhibits high decoding accuracy against various malicious attacks.

Stochastic many-body problems in ecology, evolution, neuroscience, and systems biology

NASA Astrophysics Data System (ADS)

Butler, Thomas C.

Using the tools of many-body theory, I analyze problems in four different areas of biology dominated by strong fluctuations: The evolutionary history of the genetic code, spatiotemporal pattern formation in ecology, spatiotemporal pattern formation in neuroscience and the robustness of a model circadian rhythm circuit in systems biology. In the first two research chapters, I demonstrate that the genetic code is extremely optimal (in the sense that it manages the effects of point mutations or mistranslations efficiently), more than an order of magnitude beyond what was previously thought. I further show that the structure of the genetic code implies that early proteins were probably only loosely defined. Both the nature of early proteins and the extreme optimality of the genetic code are interpreted in light of recent theory [1] as evidence that the evolution of the genetic code was driven by evolutionary dynamics that were dominated by horizontal gene transfer. I then explore the optimality of a proposed precursor to the genetic code. The results show that the precursor code has only limited optimality, which is interpreted as evidence that the precursor emerged prior to translation, or else never existed. In the next part of the dissertation, I introduce a many-body formalism for reaction-diffusion systems described at the mesoscopic scale with master equations. I first apply this formalism to spatially-extended predator-prey ecosystems, resulting in the prediction that many-body correlations and fluctuations drive population cycles in time, called quasicycles. Most of these results were previously known, but were derived using the system size expansion [2, 3]. I next apply the analytical techniques developed in the study of quasi-cycles to a simple model of Turing patterns in a predator-prey ecosystem. This analysis shows that fluctuations drive the formation of a new kind of spatiotemporal pattern formation that I name "quasi-patterns." These quasi-patterns exist over a much larger range of physically accessible parameters than the patterns predicted in mean field theory and therefore account for the apparent observations in ecology of patterns in regimes where Turing patterns do not occur. I further show that quasi-patterns have statistical properties that allow them to be distinguished empirically from mean field Turing patterns. I next analyze a model of visual cortex in the brain that has striking similarities to the activator-inhibitor model of ecosystem quasi-pattern formation. Through analysis of the resulting phase diagram, I show that the architecture of the neural network in the visual cortex is configured to make the visual cortex robust to unwanted internally generated spatial structure that interferes with normal visual function. I also predict that some geometric visual hallucinations are quasi-patterns and that the visual cortex supports a new phase of spatially scale invariant behavior present far from criticality. In the final chapter, I explore the effects of fluctuations on cycles in systems biology, specifically the pervasive phenomenon of circadian rhythms. By exploring the behavior of a generic stochastic model of circadian rhythms, I show that the circadian rhythm circuit exploits leaky mRNA production to safeguard the cycle from failure. I also show that this safeguard mechanism is highly robust to changes in the rate of leaky mRNA production. Finally, I explore the failure of the deterministic model in two different contexts, one where the deterministic model predicts cycles where they do not exist, and another context in which cycles are not predicted by the deterministic model.

Status of Artist Upgrade

DTIC Science & Technology

1988-09-01

Autodrift, ARTIST Autoscaling , Electron Density 16. PRICE CODE Profiles 17. SECURITY CLASSIFICATION 18. SECURITY CLASSIFICATION 19. SECURITY...FIGURES Figure No. Page 2.1 ARTIST Scaled Parameters 4 2.2 ARTIST ASCII Ionogram 6 2.3 ARTISTSV Optifont lonogram 7 2.4 Autoscaling of Es Trace Before...diagnostic programs for testing communication ports. The aforementioned contract required a performance evaluation of ARTIST . Manual and autoscaled

Developing a Professional Vision of Classroom Practices of a Mathematics Teacher: Views from a Researcher and a Teacher

ERIC Educational Resources Information Center

Ho, Kai Fai; Tan, Preston

2013-01-01

The term "professional vision" points to the many nuanced ways professionals see. This paper traces the development of a professional vision of a researcher and a teacher looking at classroom practices. The researcher's interest was to capture and study notable aspects of the teacher's practice. Through a coding scheme, disparate…

Reversed Field Pinch helical self-organization studies with the volume preserving field line tracing code NEMATO

NASA Astrophysics Data System (ADS)

Bonfiglio, D.; Veranda, M.; Cappello, S.; Chacon, L.; Escande, D. F.; Piovesan, P.

2009-11-01

The existence of a Reversed Field Pinch (RFP) dynamo as a (laminar) helical self-organization was anticipated by MHD numerical studies [1]. High current operation in RFX-mod experiment shows such a helical self-organization: strong internal electron transport barriers (ITB) appear and magnetic chaos healing is diagnosed when Single Helical Axis (SHAx) regimes are achieved [2]. We present results of the field line tracing code NEMATO [3] applied to study the magnetic topology resulting from 3D MHD simulations, with the aim of clarifying the conditions for chaos healing in SHAx states. First tests confirm the basic picture: the magnetic chaos due to island overlap is significantly reduced after the expulsion of the dominant mode separatrix. The possible synergy with the presence of magnetic and/or flow shear at the SHAx ITB will also be discussed [4].[4pt] [1] S. Cappello, Plasma Phys. Control. Fusion (2004) & references therein [0pt] [2] R. Lorenzini et al., Nature Phys. (2009) [0pt] [3] J. M. Finn and L. Chacon, Phys. Plasmas (2005) [0pt] [4] M.E. Puiatti et al invited presentation EPS 2009 conference, submitted to Plasma Phys. Control. Fusion

MultiElec: A MATLAB Based Application for MEA Data Analysis.

PubMed

Georgiadis, Vassilis; Stephanou, Anastasis; Townsend, Paul A; Jackson, Thomas R

2015-01-01

We present MultiElec, an open source MATLAB based application for data analysis of microelectrode array (MEA) recordings. MultiElec displays an extremely user-friendly graphic user interface (GUI) that allows the simultaneous display and analysis of voltage traces for 60 electrodes and includes functions for activation-time determination, the production of activation-time heat maps with activation time and isoline display. Furthermore, local conduction velocities are semi-automatically calculated along with their corresponding vector plots. MultiElec allows ad hoc signal suppression, enabling the user to easily and efficiently handle signal artefacts and for incomplete data sets to be analysed. Voltage traces and heat maps can be simply exported for figure production and presentation. In addition, our platform is able to produce 3D videos of signal progression over all 60 electrodes. Functions are controlled entirely by a single GUI with no need for command line input or any understanding of MATLAB code. MultiElec is open source under the terms of the GNU General Public License as published by the Free Software Foundation, version 3. Both the program and source code are available to download from http://www.cancer.manchester.ac.uk/MultiElec/.

Translational Redefinition of UGA Codons Is Regulated by Selenium Availability*

PubMed Central

Howard, Michael T.; Carlson, Bradley A.; Anderson, Christine B.; Hatfield, Dolph L.

2013-01-01

Incorporation of selenium into ∼25 mammalian selenoproteins occurs by translational recoding whereby in-frame UGA codons are redefined to encode the selenium containing amino acid, selenocysteine (Sec). Here we applied ribosome profiling to examine the effect of dietary selenium levels on the translational mechanisms controlling selenoprotein synthesis in mouse liver. Dietary selenium levels were shown to control gene-specific selenoprotein expression primarily at the translation level by differential regulation of UGA redefinition and Sec incorporation efficiency, although effects on translation initiation and mRNA abundance were also observed. Direct evidence is presented that increasing dietary selenium causes a vast increase in ribosome density downstream of UGA-Sec codons for a subset of selenoprotein mRNAs and that the selenium-dependent effects on Sec incorporation efficiency are mediated in part by the degree of Sec-tRNA[Ser]Sec Um34 methylation. Furthermore, we find evidence for translation in the 5′-UTRs for a subset of selenoproteins and for ribosome pausing near the UGA-Sec codon in those mRNAs encoding the selenoproteins most affected by selenium availability. These data illustrate how dietary levels of the trace element selenium can alter the readout of the genetic code to affect the expression of an entire class of proteins. PMID:23696641

Neural Crest Origins of the Neck and Shoulder

PubMed Central

Matsuoka, Toshiyuki; Ahlberg, Per E.; Kessaris, Nicoletta; Iannarelli, Palma; Dennehy, Ulla; Richardson, William D.; McMahon, Andrew P.; Koentges, Georgy

2005-01-01

Summary The neck and shoulder region of vertebrates has undergone a complex evolutionary history. In order to identify its underlying mechanisms we map the destinations of embryonic neural crest and mesodermal stem cells using novel Cre-recombinase mediated transgenesis. The single-cell resolution of this genetic labelling reveals cryptic cell boundaries traversing seemingly homogeneous skeleton of neck and shoulders. Within this complex assembly of bones and muscles we discern a precise code of connectivity that mesenchymal stem cells of neural crest and mesodermal origin both obey as they form muscle scaffolds. Neural crest anchors the head onto the anterior lining of the shoulder girdle, while a Hox gene controlled mesoderm links trunk muscles to the posterior neck and shoulder skeleton. The skeleton that we identify as neural crest is specifically affected in human Klippel-Feil syndrome, Sprengel’s deformity and Arnold-Chiari I/II malformation, providing first insights into their likely aetiology. We identify genes involved in the cellular modularity of neck and shoulder skeleton and propose a new methodology for determining skeletal homologies that is based on muscle attachments. This has allowed us to trace the whereabouts of the cleithrum, the major shoulder bone of extinct land vertebrate ancestors which appears to survive as the scapular spine in living mammals. PMID:16034409

The iSelect 9 K SNP analysis revealed polyploidization induced revolutionary changes and intense human selection causing strong haplotype blocks in wheat.

PubMed

Hao, Chenyang; Wang, Yuquan; Chao, Shiaoman; Li, Tian; Liu, Hongxia; Wang, Lanfen; Zhang, Xueyong

2017-01-30

A Chinese wheat mini core collection was genotyped using the wheat 9 K iSelect SNP array. Total 2420 and 2396 polymorphic SNPs were detected on the A and the B genome chromosomes, which formed 878 haplotype blocks. There were more blocks in the B genome, but the average block size was significantly (P < 0.05) smaller than those in the A genome. Intense selection (domestication and breeding) had a stronger effect on the A than on the B genome chromosomes. Based on the genetic pedigrees, many blocks can be traced back to a well-known Strampelli cross, which was made one century ago. Furthermore, polyploidization of wheat (both tetraploidization and hexaploidization) induced revolutionary changes in both the A and the B genomes, with a greater increase of gene diversity compared to their diploid ancestors. Modern breeding has dramatically increased diversity in the gene coding regions, though obvious blocks were formed on most of the chromosomes in both tetraploid and hexaploid wheats. Tag-SNP markers identified in this study can be used for marker assisted selection using haplotype blocks as a wheat breeding strategy. This strategy can also be employed to facilitate genome selection in other self-pollinating crop species.