Humans cannot consciously generate random numbers sequences: Polemic study.
Figurska, Małgorzata; Stańczyk, Maciej; Kulesza, Kamil
2008-01-01
It is widely believed, that randomness exists in Nature. In fact such an assumption underlies many scientific theories and is embedded in the foundations of quantum mechanics. Assuming that this hypothesis is valid one can use natural phenomena, like radioactive decay, to generate random numbers. Today, computers are capable of generating the so-called pseudorandom numbers. Such series of numbers are only seemingly random (bias in the randomness quality can be observed). Question whether people can produce random numbers, has been investigated by many scientists in the recent years. The paper "Humans can consciously generate random numbers sequences..." published recently in Medical Hypotheses made claims that were in many ways contrary to state of art; it also stated far-reaching hypotheses. So, we decided to repeat the experiments reported, with special care being taken of proper laboratory procedures. Here, we present the results and discuss possible implications in computer and other sciences.
Quantum random number generators
Herrero-Collantes, Miguel; Garcia-Escartin, Juan Carlos
2017-01-01
Random numbers are a fundamental resource in science and engineering with important applications in simulation and cryptography. The inherent randomness at the core of quantum mechanics makes quantum systems a perfect source of entropy. Quantum random number generation is one of the most mature quantum technologies with many alternative generation methods. This review discusses the different technologies in quantum random number generation from the early devices based on radioactive decay to the multiple ways to use the quantum states of light to gather entropy from a quantum origin. Randomness extraction and amplification and the notable possibility of generating trusted random numbers even with untrusted hardware using device-independent generation protocols are also discussed.
DEFF Research Database (Denmark)
Wanscher, Jørgen Bundgaard; Sørensen, Majken Vildrik
2006-01-01
highly uniform multidimensional draws, which are highly relevant for todays traffic models. This paper shows among others combined shuffling and scrambling seems needless, that scrambling gives the lowest correlation and that there are detectable differences between random numbers, dependent...
Hirst, Keith
1994-01-01
Number and geometry are the foundations upon which mathematics has been built over some 3000 years. This book is concerned with the logical foundations of number systems from integers to complex numbers. The author has chosen to develop the ideas by illustrating the techniques used throughout mathematics rather than using a self-contained logical treatise. The idea of proof has been emphasised, as has the illustration of concepts from a graphical, numerical and algebraic point of view. Having laid the foundations of the number system, the author has then turned to the analysis of infinite proc
absolutely regular random sequences
Directory of Open Access Journals (Sweden)
Michel Harel
1996-01-01
Full Text Available In this paper, the central limit theorems for the density estimator and for the integrated square error are proved for the case when the underlying sequence of random variables is nonstationary. Applications to Markov processes and ARMA processes are provided.
Random Numbers and Quantum Computers
McCartney, Mark; Glass, David
2002-01-01
The topic of random numbers is investigated in such a way as to illustrate links between mathematics, physics and computer science. First, the generation of random numbers by a classical computer using the linear congruential generator and logistic map is considered. It is noted that these procedures yield only pseudo-random numbers since…
Investigating the Randomness of Numbers
Pendleton, Kenn L.
2009-01-01
The use of random numbers is pervasive in today's world. Random numbers have practical applications in such far-flung arenas as computer simulations, cryptography, gambling, the legal system, statistical sampling, and even the war on terrorism. Evaluating the randomness of extremely large samples is a complex, intricate process. However, the…
Thermodynamics of random number generation
Aghamohammadi, Cina; Crutchfield, James P.
2017-06-01
We analyze the thermodynamic costs of the three main approaches to generating random numbers via the recently introduced Information Processing Second Law. Given access to a specified source of randomness, a random number generator (RNG) produces samples from a desired target probability distribution. This differs from pseudorandom number generators (PRNGs) that use wholly deterministic algorithms and from true random number generators (TRNGs) in which the randomness source is a physical system. For each class, we analyze the thermodynamics of generators based on algorithms implemented as finite-state machines, as these allow for direct bounds on the required physical resources. This establishes bounds on heat dissipation and work consumption during the operation of three main classes of RNG algorithms—including those of von Neumann, Knuth, and Yao and Roche and Hoshi—and for PRNG methods. We introduce a general TRNG and determine its thermodynamic costs exactly for arbitrary target distributions. The results highlight the significant differences between the three main approaches to random number generation: One is work producing, one is work consuming, and the other is potentially dissipation neutral. Notably, TRNGs can both generate random numbers and convert thermal energy to stored work. These thermodynamic costs on information creation complement Landauer's limit on the irreducible costs of information destruction.
Random Numbers from Astronomical Imaging
Pimbblet, Kevin A.; Bulmer, Michael
2004-01-01
This article describes a method to turn astronomical imaging into a random number generator by using the positions of incident cosmic rays and hot pixels to generate bit streams. We subject the resultant bit streams to a battery of standard benchmark statistical tests for randomness and show that these bit streams are statistically the same as a perfect random bit stream. Strategies for improving and building upon this method are outlined.
Random numbers spring from alpha decay
Energy Technology Data Exchange (ETDEWEB)
Frigerio, N.A.; Sanathanan, L.P.; Morley, M.; Clark, N.A.; Tyler, S.A.
1980-05-01
Congruential random number generators, which are widely used in Monte Carlo simulations, are deficient in that the number they generate are concentrated in a relatively small number of hyperplanes. While this deficiency may not be a limitation in small Monte Carlo studies involving a few variables, it introduces a significant bias in large simulations requiring high resolution. This bias was recognized and assessed during preparations for an accident analysis study of nuclear power plants. This report describes a random number device based on the radioactive decay of alpha particles from a /sup 235/U source in a high-resolution gas proportional counter. The signals were fed to a 4096-channel analyzer and for each channel the frequency of signals registered in a 20,000-microsecond interval was recorded. The parity bits of these frequency counts (0 for an even count and 1 for an odd count) were then assembled in sequence to form 31-bit binary random numbers and transcribed to a magnetic tape. This cycle was repeated as many times as were necessary to create 3 million random numbers. The frequency distribution of counts from the present device conforms to the Brockwell-Moyal distribution, which takes into account the dead time of the counter (both the dead time and decay constant of the underlying Poisson process were estimated). Analysis of the count data and tests of randomness on a sample set of the 31-bit binary numbers indicate that this random number device is a highly reliable source of truly random numbers. Its use is, therefore, recommended in Monte Carlo simulations for which the congruential pseudorandom number generators are found to be inadequate. 6 figures, 5 tables.
Sequence Factorial of "g"-Gonal Numbers
Asiru, Muniru A.
2013-01-01
The gamma function, which has the property to interpolate the factorial whenever the argument is an integer, is a special case (the case "g"?=?2) of the general term of the sequence factorial of "g"-gonal numbers. In relation to this special case, a formula for calculating the general term of the sequence factorial of any…
Permutation Entropy for Random Binary Sequences
Directory of Open Access Journals (Sweden)
Lingfeng Liu
2015-12-01
Full Text Available In this paper, we generalize the permutation entropy (PE measure to binary sequences, which is based on Shannon’s entropy, and theoretically analyze this measure for random binary sequences. We deduce the theoretical value of PE for random binary sequences, which can be used to measure the randomness of binary sequences. We also reveal the relationship between this PE measure with other randomness measures, such as Shannon’s entropy and Lempel–Ziv complexity. The results show that PE is consistent with these two measures. Furthermore, we use PE as one of the randomness measures to evaluate the randomness of chaotic binary sequences.
Self-correcting random number generator
Energy Technology Data Exchange (ETDEWEB)
Humble, Travis S.; Pooser, Raphael C.
2016-09-06
A system and method for generating random numbers. The system may include a random number generator (RNG), such as a quantum random number generator (QRNG) configured to self-correct or adapt in order to substantially achieve randomness from the output of the RNG. By adapting, the RNG may generate a random number that may be considered random regardless of whether the random number itself is tested as such. As an example, the RNG may include components to monitor one or more characteristics of the RNG during operation, and may use the monitored characteristics as a basis for adapting, or self-correcting, to provide a random number according to one or more performance criteria.
Analysis of android random number generator
Sarıtaş, Serkan
2013-01-01
Ankara : The Department of Computer Engineering and the Graduate School of Engineering and Science of Bilkent University, 2013. Thesis (Master's) -- Bilkent University, 2013. Includes bibliographical references leaves 61-65. Randomness is a crucial resource for cryptography, and random number generators are critical building blocks of almost all cryptographic systems. Therefore, random number generation is one of the key parts of secure communication. Random number generatio...
Hurdles in Acquiring the Number Word Sequence
Gould, Peter
2016-01-01
Learning the sequence of number words in English up to 30 is not a simple process. In NSW government schools taking part in "Early Action for Success," over 800 students in each of the first 3 years of school were assessed every 5 weeks over the school year to determine the highest correct oral count they could produce. Rather than…
Pseudo-random number generator based on asymptotic deterministic randomness
Energy Technology Data Exchange (ETDEWEB)
Wang Kai [Department of Radio Engineering, Southeast University, Nanjing (China)], E-mail: kaiwang@seu.edu.cn; Pei Wenjiang; Xia Haishan [Department of Radio Engineering, Southeast University, Nanjing (China); Cheung Yiuming [Department of Computer Science, Hong Kong Baptist University, Hong Kong (China)
2008-06-09
A novel approach to generate the pseudorandom-bit sequence from the asymptotic deterministic randomness system is proposed in this Letter. We study the characteristic of multi-value correspondence of the asymptotic deterministic randomness constructed by the piecewise linear map and the noninvertible nonlinearity transform, and then give the discretized systems in the finite digitized state space. The statistic characteristics of the asymptotic deterministic randomness are investigated numerically, such as stationary probability density function and random-like behavior. Furthermore, we analyze the dynamics of the symbolic sequence. Both theoretical and experimental results show that the symbolic sequence of the asymptotic deterministic randomness possesses very good cryptographic properties, which improve the security of chaos based PRBGs and increase the resistance against entropy attacks and symbolic dynamics attacks.
Simulations Using Random-Generated DNA and RNA Sequences
Bryce, C. F. A.
1977-01-01
Using a very simple computer program written in BASIC, a very large number of random-generated DNA or RNA sequences are obtained. Students use these sequences to predict complementary sequences and translational products, evaluate base compositions, determine frequencies of particular triplet codons, and suggest possible secondary structures.…
Source-Independent Quantum Random Number Generation
Cao, Zhu; Zhou, Hongyi; Yuan, Xiao; Ma, Xiongfeng
2016-01-01
Quantum random number generators can provide genuine randomness by appealing to the fundamental principles of quantum mechanics. In general, a physical generator contains two parts—a randomness source and its readout. The source is essential to the quality of the resulting random numbers; hence, it needs to be carefully calibrated and modeled to achieve information-theoretical provable randomness. However, in practice, the source is a complicated physical system, such as a light source or an atomic ensemble, and any deviations in the real-life implementation from the theoretical model may affect the randomness of the output. To close this gap, we propose a source-independent scheme for quantum random number generation in which output randomness can be certified, even when the source is uncharacterized and untrusted. In our randomness analysis, we make no assumptions about the dimension of the source. For instance, multiphoton emissions are allowed in optical implementations. Our analysis takes into account the finite-key effect with the composable security definition. In the limit of large data size, the length of the input random seed is exponentially small compared to that of the output random bit. In addition, by modifying a quantum key distribution system, we experimentally demonstrate our scheme and achieve a randomness generation rate of over 5 ×103 bit /s .
Brain potentials index executive functions during random number generation.
Joppich, Gregor; Däuper, Jan; Dengler, Reinhard; Johannes, Sönke; Rodriguez-Fornells, Antoni; Münte, Thomas F
2004-06-01
The generation of random sequences is considered to tax different executive functions. To explore the involvement of these functions further, brain potentials were recorded in 16 healthy young adults while either engaging in random number generation (RNG) by pressing the number keys on a computer keyboard in a random sequence or in ordered number generation (ONG) necessitating key presses in the canonical order. Key presses were paced by an external auditory stimulus to yield either fast (1 press/800 ms) or slow (1 press/1300 ms) sequences in separate runs. Attentional demands of random and ordered tasks were assessed by the introduction of a secondary task (key-press to a target tone). The P3 amplitude to the target tone of this secondary task was reduced during RNG, reflecting the greater consumption of attentional resources during RNG. Moreover, RNG led to a left frontal negativity peaking 140 ms after the onset of the pacing stimulus, whenever the subjects produced a true random response. This negativity could be attributed to the left dorsolateral prefrontal cortex and was absent when numbers were repeated. This negativity was interpreted as an index for the inhibition of habitual responses. Finally, in response locked ERPs a negative component was apparent peaking about 50 ms after the key-press that was more prominent during RNG. Source localization suggested a medial frontal source. This effect was tentatively interpreted as a reflection of the greater monitoring demands during random sequence generation.
Random Number Generators in Secure Disk Drives
Directory of Open Access Journals (Sweden)
Hars Laszlo
2009-01-01
Full Text Available Abstract Cryptographic random number generators seeded by physical entropy sources are employed in many embedded security systems, including self-encrypting disk drives, being manufactured by the millions every year. Random numbers are used for generating encryption keys and for facilitating secure communication, and they are also provided to users for their applications. We discuss common randomness requirements, techniques for estimating the entropy of physical sources, investigate specific nonrandom physical properties, estimate the autocorrelation, then mix reduce the data until all common randomness tests pass. This method is applied to a randomness source in disk drives: the always changing coefficients of an adaptive filter for the read channel equalization. These coefficients, affected by many kinds of physical noise, are used in the reseeding process of a cryptographic pseudorandom number generator in a family of self encrypting disk drives currently in the market.
Random numbers certified by Bell's theorem.
Pironio, S; Acín, A; Massar, S; de la Giroday, A Boyer; Matsukevich, D N; Maunz, P; Olmschenk, S; Hayes, D; Luo, L; Manning, T A; Monroe, C
2010-04-15
Randomness is a fundamental feature of nature and a valuable resource for applications ranging from cryptography and gambling to numerical simulation of physical and biological systems. Random numbers, however, are difficult to characterize mathematically, and their generation must rely on an unpredictable physical process. Inaccuracies in the theoretical modelling of such processes or failures of the devices, possibly due to adversarial attacks, limit the reliability of random number generators in ways that are difficult to control and detect. Here, inspired by earlier work on non-locality-based and device-independent quantum information processing, we show that the non-local correlations of entangled quantum particles can be used to certify the presence of genuine randomness. It is thereby possible to design a cryptographically secure random number generator that does not require any assumption about the internal working of the device. Such a strong form of randomness generation is impossible classically and possible in quantum systems only if certified by a Bell inequality violation. We carry out a proof-of-concept demonstration of this proposal in a system of two entangled atoms separated by approximately one metre. The observed Bell inequality violation, featuring near perfect detection efficiency, guarantees that 42 new random numbers are generated with 99 per cent confidence. Our results lay the groundwork for future device-independent quantum information experiments and for addressing fundamental issues raised by the intrinsic randomness of quantum theory.
Astronomical random numbers for quantum foundations experiments
Leung, Calvin; Brown, Amy; Nguyen, Hien; Friedman, Andrew S.; Kaiser, David I.; Gallicchio, Jason
2017-01-01
Photons from distant astronomical sources can be used as a classical source of randomness to improve fundamental tests of quantum nonlocality, wave-particle duality, and local realism through Bell's inequality and delayed-choice quantum eraser tests inspired by Wheeler's cosmic-scale Mach-Zehnder interferometer gedankenexperiment. Such sources of random numbers may also be useful for information-theoretic applications such as key distribution for quantum cryptography. Building on the design o...
New Design of Crypto-Based Pseudo random number generator (CBPRNG) using BLOW FISH cipher
T.Chalama Reddy; Dr.R.Seshadri
2013-01-01
Random Number Generators (RNGs) are an important building block for algorithms and protocols in cryptography. Random number generation is used in a wide variety of cryptographic operations, such as key generation and challenge/response protocols. A random number generator outputs a sequence of 0s and 1s such that at any position, the next bit cannot be expected on the previous bits. However, true random number produces non- deterministic output since if the same random generator is run twice,...
A Hybrid Random Number Generator(HRNG
Directory of Open Access Journals (Sweden)
Osvaldo Skliar
2011-07-01
Full Text Available The purpose of this paper is to present a novel Hybrid Random Number Generator (HRNG. Here “hybrid” refers to the fact that to construct this generator it is necessary to use 1physical components – texts – and a physical process, and 2 a mathematical procedure. This HRNG makes it possible to generate genuine random numbers which may be used both for computer simulation of probabilistic systems and in the field of cryptography. The results of a comparative study of the binary strings generated by this HRNG and of those generated by two highly used implementations of a congruential algorithm designed to generate pseudorandom numbers are given here. One of the latter is the implementation incorporated into the Java 2 platform (version 1.6, and the other is the implementation incorporated into the runtime library of Microsoft’s Visual C++ 2008 compiler.
Chromosome number9 specific repetitive DNA sequence
Energy Technology Data Exchange (ETDEWEB)
Joste, N.E.; Cram, L.S.; Hildebrand, C.E.; Jones, M.; Longmire, J.; Robinson, T.; Moyzis, R.K.
1986-05-01
Human repetitive DNA libraries have been constructed and various recombinant DNA clones isolated that are likely candidates for chromosome specific sequences. The first clone tested (pHuR 98; plasmid human repeat 98) was biotinylated and hybridized to human chromosomes in situ. The hybridized recombinant probe was detected with fluoresceinated avidin, and chromosomes were counter-stained with either propidium iodide or distamycin-DAPI. Specific hybridization to chromosome band 9q1 was obtained. The localization was confirmed by hybridizing radiolabeled pHuR 98 DNA to human chromosomes sorted by flow cytometry. Various methods, including orthogonal field pulsed gel electrophoresis analysis indicate that 75 kilobase blocks of this sequence are interspersed with other repetitive DNA sequences in this chromosome band. This study is the first to report a human repetitive DNA sequence uniquely localized to a specific chromosome. This clone provides an easily detected and highly specific chromosomal marker for molecular cytogenetic analyses in numerous basic research and clinical studies.
Generation of Random Numbers and Parallel Random Number Streams for Monte Carlo Simulations
Directory of Open Access Journals (Sweden)
L. Yu. Barash
2012-01-01
Full Text Available Modern methods and libraries for high quality pseudorandom number generation and for generation of parallel random number streams for Monte Carlo simulations are considered. The probability equidistribution property and the parameters when the property holds at dimensions up to logarithm of mesh size are considered for Multiple Recursive Generators.
Analysis of entropy extraction efficiencies in random number generation systems
Wang, Chao; Wang, Shuang; Chen, Wei; Yin, Zhen-Qiang; Han, Zheng-Fu
2016-05-01
Random numbers (RNs) have applications in many areas: lottery games, gambling, computer simulation, and, most importantly, cryptography [N. Gisin et al., Rev. Mod. Phys. 74 (2002) 145]. In cryptography theory, the theoretical security of the system calls for high quality RNs. Therefore, developing methods for producing unpredictable RNs with adequate speed is an attractive topic. Early on, despite the lack of theoretical support, pseudo RNs generated by algorithmic methods performed well and satisfied reasonable statistical requirements. However, as implemented, those pseudorandom sequences were completely determined by mathematical formulas and initial seeds, which cannot introduce extra entropy or information. In these cases, “random” bits are generated that are not at all random. Physical random number generators (RNGs), which, in contrast to algorithmic methods, are based on unpredictable physical random phenomena, have attracted considerable research interest. However, the way that we extract random bits from those physical entropy sources has a large influence on the efficiency and performance of the system. In this manuscript, we will review and discuss several randomness extraction schemes that are based on radiation or photon arrival times. We analyze the robustness, post-processing requirements and, in particular, the extraction efficiency of those methods to aid in the construction of efficient, compact and robust physical RNG systems.
Comparison theorems for summability methods of sequences of fuzzy numbers
Yavuz, Enes
2016-01-01
In this study we compare Ces\\`{a}ro and Euler weighted mean methods of summability of sequences of fuzzy numbers with Abel and Borel power series methods of summability of sequences of fuzzy numbers. Also some results dealing with series of fuzzy numbers are obtained.
Cellular Automata-Based Parallel Random Number Generators Using FPGAs
Directory of Open Access Journals (Sweden)
David H. K. Hoe
2012-01-01
Full Text Available Cellular computing represents a new paradigm for implementing high-speed massively parallel machines. Cellular automata (CA, which consist of an array of locally connected processing elements, are a basic form of a cellular-based architecture. The use of field programmable gate arrays (FPGAs for implementing CA accelerators has shown promising results. This paper investigates the design of CA-based pseudo-random number generators (PRNGs using an FPGA platform. To improve the quality of the random numbers that are generated, the basic CA structure is enhanced in two ways. First, the addition of a superrule to each CA cell is considered. The resulting self-programmable CA (SPCA uses the superrule to determine when to make a dynamic rule change in each CA cell. The superrule takes its inputs from neighboring cells and can be considered itself a second CA working in parallel with the main CA. When implemented on an FPGA, the use of lookup tables in each logic cell removes any restrictions on how the super-rules should be defined. Second, a hybrid configuration is formed by combining a CA with a linear feedback shift register (LFSR. This is advantageous for FPGA designs due to the compactness of the LFSR implementations. A standard software package for statistically evaluating the quality of random number sequences known as Diehard is used to validate the results. Both the SPCA and the hybrid CA/LFSR were found to pass all the Diehard tests.
Nonlinear deterministic structures and the randomness of protein sequences
Huang Yan Zhao
2003-01-01
To clarify the randomness of protein sequences, we make a detailed analysis of a set of typical protein sequences representing each structural classes by using nonlinear prediction method. No deterministic structures are found in these protein sequences and this implies that they behave as random sequences. We also give an explanation to the controversial results obtained in previous investigations.
Multi-bit quantum random number generation by measuring positions of arrival photons.
Yan, Qiurong; Zhao, Baosheng; Liao, Qinghong; Zhou, Nanrun
2014-10-01
We report upon the realization of a novel multi-bit optical quantum random number generator by continuously measuring the arrival positions of photon emitted from a LED using MCP-based WSA photon counting imaging detector. A spatial encoding method is proposed to extract multi-bits random number from the position coordinates of each detected photon. The randomness of bits sequence relies on the intrinsic randomness of the quantum physical processes of photonic emission and subsequent photoelectric conversion. A prototype has been built and the random bit generation rate could reach 8 Mbit/s, with random bit generation efficiency of 16 bits per detected photon. FPGA implementation of Huffman coding is proposed to reduce the bias of raw extracted random bits. The random numbers passed all tests for physical random number generator.
Random Numbers Generated from Audio and Video Sources
Directory of Open Access Journals (Sweden)
I-Te Chen
2013-01-01
Full Text Available Random numbers are very useful in simulation, chaos theory, game theory, information theory, pattern recognition, probability theory, quantum mechanics, statistics, and statistical mechanics. The random numbers are especially helpful in cryptography. In this work, the proposed random number generators come from white noise of audio and video (A/V sources which are extracted from high-resolution IPCAM, WEBCAM, and MPEG-1 video files. The proposed generator applied on video sources from IPCAM and WEBCAM with microphone would be the true random number generator and the pseudorandom number generator when applied on video sources from MPEG-1 video file. In addition, when applying NIST SP 800-22 Rev.1a 15 statistics tests on the random numbers generated from the proposed generator, around 98% random numbers can pass 15 statistical tests. Furthermore, the audio and video sources can be found easily; hence, the proposed generator is a qualified, convenient, and efficient random number generator.
The domination number of a random graph
DEFF Research Database (Denmark)
Henning, Michael A.; Yeo, Anders
2014-01-01
The domination number γ(G) of a graph G is the minimum cardinality of a set S of vertices so that every vertex outside S is adjacent to a vertex in S, while its total domination number γt(G) is the minimum cardinality of a set S of vertices so that every vertex in the graph is adjacent to a vertex...
Cryptographic pseudo-random sequences from the chaotic Hénon ...
Indian Academy of Sciences (India)
Pseudo-random number sequences are useful in many applications including Monte-Carlo simulation, spread spectrum ... a pseudo-random binary sequence from the two-dimensional chaotic Hénon map is explored. ... is the Hénon map, a two-dimensional discrete-time nonlinear dynamical system represented by the state ...
Analysis of Additive Random Number Generators.
1977-03-01
CLASSIFICATION OF THIS PAGE (When Data Entered; I .,.,•• n .„^iMl~^.-». H .,il~l.*...,...-•..,.,.., • 1 ——’"- •"•’ ANALYSIS OF ADDITIVE RANDOM...among my teachers two of the best: my parents, Bil and Marleen Reiser. - , i — - •- - J I " ii. .1 I l. Kl U...the period, we know that r(pa*z) * pr(pa) and k - • - ----• •--- - -— — ...., . H ..J 1-..11.111 ’ Introduction that r(pa *’) divides
Unbiased All-Optical Random-Number Generator
Tobias Steinle; Greiner, Johannes N.; Jörg Wrachtrup; Harald Giessen; Ilja Gerhardt
2017-01-01
The generation of random bits is of enormous importance in modern information science. Cryptographic security is based on random numbers which require a physical process for their generation. This is commonly performed by hardware random number generators. These exhibit often a number of problems, namely experimental bias, memory in the system, and other technical subtleties, which reduce the reliability in the entropy estimation. Further, the generated outcome has to be post-processed to "ir...
Mapping copy number variation by population-scale genome sequencing
DEFF Research Database (Denmark)
Mills, Ryan E.; Walter, Klaudia; Stewart, Chip
2011-01-01
, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications...... differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies....
Laugier, Alexandre; Saikia, Manjil P.
2012-01-01
In this paper we study the Fibonacci numbers and derive some interesting properties and recurrence relations. We prove some charecterizations for $F_p$, where $p$ is a prime of a certain type. We also define period of a Fibonacci sequence modulo an integer, $m$ and derive certain interesting properties related to them. Afterwards, we derive some new properties of a class of generalized Fibonacci numbers. In the last part of the paper we introduce some generalized Fibonacci polynomial sequence...
Random number datasets generated from statistical analysis of randomly sampled GSM recharge cards.
Okagbue, Hilary I; Opanuga, Abiodun A; Oguntunde, Pelumi E; Ugwoke, Paulinus O
2017-02-01
In this article, a random number of datasets was generated from random samples of used GSM (Global Systems for Mobile Communications) recharge cards. Statistical analyses were performed to refine the raw data to random number datasets arranged in table. A detailed description of the method and relevant tests of randomness were also discussed.
A Comparison of Three Random Number Generators for Aircraft Dynamic Modeling Applications
Grauer, Jared A.
2017-01-01
Three random number generators, which produce Gaussian white noise sequences, were compared to assess their suitability in aircraft dynamic modeling applications. The first generator considered was the MATLAB (registered) implementation of the Mersenne-Twister algorithm. The second generator was a website called Random.org, which processes atmospheric noise measured using radios to create the random numbers. The third generator was based on synthesis of the Fourier series, where the random number sequences are constructed from prescribed amplitude and phase spectra. A total of 200 sequences, each having 601 random numbers, for each generator were collected and analyzed in terms of the mean, variance, normality, autocorrelation, and power spectral density. These sequences were then applied to two problems in aircraft dynamic modeling, namely estimating stability and control derivatives from simulated onboard sensor data, and simulating flight in atmospheric turbulence. In general, each random number generator had good performance and is well-suited for aircraft dynamic modeling applications. Specific strengths and weaknesses of each generator are discussed. For Monte Carlo simulation, the Fourier synthesis method is recommended because it most accurately and consistently approximated Gaussian white noise and can be implemented with reasonable computational effort.
Understanding Number Sequences Leads to Understanding Mathematics Concepts
Pasnak, Robert; Schmerold, Katrina Lea; Robinson, Melissa Fetterer; Gadzichowski, K. Marinka; Bock, Allison M.; O'Brien, Sarah Eva; Kidd, Julie K.; Gallington, Deb A.
2016-01-01
Ninety-six first grade students in an urban school system were tested in October and May on reading, mathematics, and their understanding of sequences of letters and numbers. A time lag analysis was subsequently conducted. In such analyses, cross-correlations between the first measurement of one variable and the second measurement of another are…
Cluster growing process and a sequence of magic numbers
DEFF Research Database (Denmark)
Solov'yov, Ilia; Solov'yov, Andrey V.; Greiner, Walter
2003-01-01
demonstrate that in this way all known global minimum structures of the Lennard-Jones (LJ) clusters can be found. Our method provides an efficient tool for the calculation and analysis of atomic cluster structure. With its use we justify the magic number sequence for the clusters of noble gas atoms...
Comparative Copy Number Variation From Whole Genome Sequencing
Janevski, A.; Varadan, V.; Kamalakaran, S.; Banerjee, N.; Dimitrova, D.
2011-01-01
Whole genome sequencing enables a high resolution view of the humangenome and enables unique insights into copy number variations in anunprecedented scale. Numerous tools and studies have already been introduced that provide confirmatory and new genomic variability datain individuals and across
The resulting node number sequence may increase the bandwidth ...
Indian Academy of Sciences (India)
204 N Ramakrishnan, T_ Balakrishna Bhat and V S Arunachalam point of intersection and the nodal and elemental directories are appropriately altered. The resulting node number sequence may increase the bandwidth of the stiffness matrix. Therefore the region of interest is scanned and the nodal and the elemental.
Random Sequence for Optimal Low-Power Laser Generated Ultrasound
Vangi, D.; Virga, A.; Gulino, M. S.
2017-08-01
Low-power laser generated ultrasounds are lately gaining importance in the research world, thanks to the possibility of investigating a mechanical component structural integrity through a non-contact and Non-Destructive Testing (NDT) procedure. The ultrasounds are, however, very low in amplitude, making it necessary to use pre-processing and post-processing operations on the signals to detect them. The cross-correlation technique is used in this work, meaning that a random signal must be used as laser input. For this purpose, a highly random and simple-to-create code called T sequence, capable of enhancing the ultrasound detectability, is introduced (not previously available at the state of the art). Several important parameters which characterize the T sequence can influence the process: the number of pulses Npulses , the pulse duration δ and the distance between pulses dpulses . A Finite Element FE model of a 3 mm steel disk has been initially developed to analytically study the longitudinal ultrasound generation mechanism and the obtainable outputs. Later, experimental tests have shown that the T sequence is highly flexible for ultrasound detection purposes, making it optimal to use high Npulses and δ but low dpulses . In the end, apart from describing all phenomena that arise in the low-power laser generation process, the results of this study are also important for setting up an effective NDT procedure using this technology.
Random Number Generation for Petascale Quantum Monte Carlo
Energy Technology Data Exchange (ETDEWEB)
Ashok Srinivasan
2010-03-16
The quality of random number generators can affect the results of Monte Carlo computations, especially when a large number of random numbers are consumed. Furthermore, correlations present between different random number streams in a parallel computation can further affect the results. The SPRNG software, which the author had developed earlier, has pseudo-random number generators (PRNGs) capable of producing large numbers of streams with large periods. However, they had been empirically tested on only thousand streams earlier. In the work summarized here, we tested the SPRNG generators with over a hundred thousand streams, involving over 10^14 random numbers per test, on some tests. We also tested the popular Mersenne Twister. We believe that these are the largest tests of PRNGs, both in terms of the numbers of streams tested and the number of random numbers tested. We observed defects in some of these generators, including the Mersenne Twister, while a few generators appeared to perform well. We also corrected an error in the implementation of one of the SPRNG generators.
Estimation of copy number alterations from exome sequencing data.
Directory of Open Access Journals (Sweden)
Rafael Valdés-Mas
Full Text Available Exome sequencing constitutes an important technology for the study of human hereditary diseases and cancer. However, the ability of this approach to identify copy number alterations in primary tumor samples has not been fully addressed. Here we show that somatic copy number alterations can be reliably estimated using exome sequencing data through a strategy that we have termed exome2cnv. Using data from 86 paired normal and primary tumor samples, we identified losses and gains of complete chromosomes or large genomic regions, as well as smaller regions affecting a minimum of one gene. Comparison with high-resolution comparative genomic hybridization (CGH arrays revealed a high sensitivity and a low number of false positives in the copy number estimation between both approaches. We explore the main factors affecting sensitivity and false positives with real data, and provide a side by side comparison with CGH arrays. Together, these results underscore the utility of exome sequencing to study cancer samples by allowing not only the identification of substitutions and indels, but also the accurate estimation of copy number alterations.
Quantum Random Number Generation on a Mobile Phone
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Bruno Sanguinetti
2014-09-01
Full Text Available Quantum random number generators (QRNGs can significantly improve the security of cryptographic protocols by ensuring that generated keys cannot be predicted. However, the cost, size, and power requirements of current Quantum random number generators have prevented them from becoming widespread. In the meantime, the quality of the cameras integrated in mobile telephones has improved significantly so that now they are sensitive to light at the few-photon level. We demonstrate how these can be used to generate random numbers of a quantum origin.
Münte, Thomas F; Joppich, Gregor; Däuper, Jan; Schrader, Christoph; Dengler, Reinhard; Heldmann, Marcus
2015-01-01
The generation of random sequences is considered to tax executive functions and has been reported to be impaired in Parkinson's disease (PD) previously. To assess the neurophysiological markers of random number generation in PD. Event-related potentials (ERP) were recorded in 12 PD patients and 12 age-matched normal controls (NC) while either engaging in random number generation (RNG) by pressing the number keys on a computer keyboard in a random sequence or in ordered number generation (ONG) necessitating key presses in the canonical order. Key presses were paced by an external auditory stimulus at a rate of 1 tone every 1800 ms. As a secondary task subjects had to monitor the tone-sequence for a particular target tone to which the number "0" key had to be pressed. This target tone occurred randomly and infrequently, thus creating a secondary oddball task. Behaviorally, PD patients showed an increased tendency to count in steps of one as well as a tendency towards repetition avoidance. Electrophysiologically, the amplitude of the P3 component of the ERP to the target tone of the secondary task was reduced during RNG in PD but not in NC. The behavioral findings indicate less random behavior in PD while the ERP findings suggest that this impairment comes about, because attentional resources are depleted in PD.
Recoverable Random Numbers in an Internet of Things Operating System
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Taeill Yoo
2017-03-01
Full Text Available Over the past decade, several security issues with Linux Random Number Generator (LRNG on PCs and Androids have emerged. The main problem involves the process of entropy harvesting, particularly at boot time. An entropy source in the input pool of LRNG is not transferred into the non-blocking output pool if the entropy counter of the input pool is less than 192 bits out of 4098 bits. Because the entropy estimation of LRNG is highly conservative, the process may require more than one minute for starting the transfer. Furthermore, the design principle of the estimation algorithm is not only heuristic but also unclear. Recently, Google released an Internet of Things (IoT operating system called Brillo based on the Linux kernel. We analyze the behavior of the random number generator in Brillo, which inherits that of LRNG. In the results, we identify two features that enable recovery of random numbers. With these features, we demonstrate that random numbers of 700 bytes at boot time can be recovered with the success probability of 90% by using time complexity for 5.20 × 2 40 trials. Therefore, the entropy of random numbers of 700 bytes is merely about 43 bits. Since the initial random numbers are supposed to be used for sensitive security parameters, such as stack canary and key derivation, our observation can be applied to practical attacks against cryptosystem.
On the design of henon and logistic map-based random number generator
Magfirawaty; Suryadi, M. T.; Ramli, Kalamullah
2017-10-01
The key sequence is one of the main elements in the cryptosystem. True Random Number Generators (TRNG) method is one of the approaches to generating the key sequence. The randomness source of the TRNG divided into three main groups, i.e. electrical noise based, jitter based and chaos based. The chaos based utilizes a non-linear dynamic system (continuous time or discrete time) as an entropy source. In this study, a new design of TRNG based on discrete time chaotic system is proposed, which is then simulated in LabVIEW. The principle of the design consists of combining 2D and 1D chaotic systems. A mathematical model is implemented for numerical simulations. We used comparator process as a harvester method to obtain the series of random bits. Without any post processing, the proposed design generated random bit sequence with high entropy value and passed all NIST 800.22 statistical tests.
A Bidirectional Generalized Synchronization Theorem-Based Chaotic Pseudo-random Number Generator
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Han Shuangshuang
2013-07-01
Full Text Available Based on a bidirectional generalized synchronization theorem for discrete chaos system, this paper introduces a new 5-dimensional bidirectional generalized chaos synchronization system (BGCSDS, whose prototype is a novel chaotic system introduced in [12]. Numerical simulation showed that two pair variables of the BGCSDS achieve generalized chaos synchronization via a transform H.A chaos-based pseudo-random number generator (CPNG was designed by the new BGCSDS. Using the FIPS-140-2 tests issued by the National Institute of Standard and Technology (NIST verified the randomness of the 1000 binary number sequences generated via the CPNG and the RC4 algorithm respectively. The results showed that all the tested sequences passed the FIPS-140-2 tests. The confidence interval analysis showed the statistical properties of the randomness of the sequences generated via the CPNG and the RC4 algorithm do not have significant differences.
Ternary jitter-based true random number generator
Latypov, Rustam; Stolov, Evgeni
2017-01-01
In this paper a novel family of generators producing true uniform random numbers in ternary logic is presented. The generator consists of a number of identical ternary logic combinational units connected into a ring. All the units are provided to have a random delay time, and this time is supposed to be distributed in accordance with an exponential distribution. All delays are supposed to be independent events. The theory of the generator is based on Erlang equations. The generator can be used for test production in various systems. Features of multidimensional random vectors, produced by the generator, are discussed.
On the variance of the number of real zeros of a random trigonometric polynomial
Directory of Open Access Journals (Sweden)
K. Farahmand
1997-01-01
is a sequence of independent normally distributed random variables is known. The present paper provides an upper estimate for the variance of such a number. To achieve this result we first present a general formula for the covariance of the number of real zeros of any normal process, ξ(t, occurring in any two disjoint intervals. A formula for the variance of the number of real zeros of ξ(t follows from this result.
Delay line length selection in generating fast random numbers with a chaotic laser.
Zhang, Jianzhong; Wang, Yuncai; Xue, Lugang; Hou, Jiayin; Zhang, Beibei; Wang, Anbang; Zhang, Mingjiang
2012-04-10
The chaotic light signals generated by an external cavity semiconductor laser have been experimentally demonstrated to extract fast random numbers. However, the photon round-trip time in the external cavity can cause the occurrence of the periodicity in random sequences. To overcome it, the exclusive-or operation on corresponding random bits in samples of the chaotic signal and its time-delay signal from a chaotic laser is required. In this scheme, the proper selection of delay length is a key issue. By doing a large number of experiments and theoretically analyzing the interplay between the Runs test and the threshold value of the autocorrelation function, we find when the corresponding delay time of autocorrelation trace with the correlation coefficient of less than 0.007 is considered as the delay time between the chaotic signal and its time-delay signal, streams of random numbers can be generated with verified randomness.
On the number of spanning trees in random regular graphs
DEFF Research Database (Denmark)
Greenhill, Catherine; Kwan, Matthew; Wind, David Kofoed
2014-01-01
Let d >= 3 be a fixed integer. We give an asympotic formula for the expected number of spanning trees in a uniformly random d-regular graph with n vertices. (The asymptotics are as n -> infinity, restricted to even n if d is odd.) We also obtain the asymptotic distribution of the number of spanni...
Unbiased All-Optical Random-Number Generator
Steinle, Tobias; Greiner, Johannes N.; Wrachtrup, Jörg; Giessen, Harald; Gerhardt, Ilja
2017-10-01
The generation of random bits is of enormous importance in modern information science. Cryptographic security is based on random numbers which require a physical process for their generation. This is commonly performed by hardware random-number generators. These often exhibit a number of problems, namely experimental bias, memory in the system, and other technical subtleties, which reduce the reliability in the entropy estimation. Further, the generated outcome has to be postprocessed to "iron out" such spurious effects. Here, we present a purely optical randomness generator, based on the bistable output of an optical parametric oscillator. Detector noise plays no role and postprocessing is reduced to a minimum. Upon entering the bistable regime, initially the resulting output phase depends on vacuum fluctuations. Later, the phase is rigidly locked and can be well determined versus a pulse train, which is derived from the pump laser. This delivers an ambiguity-free output, which is reliably detected and associated with a binary outcome. The resulting random bit stream resembles a perfect coin toss and passes all relevant randomness measures. The random nature of the generated binary outcome is furthermore confirmed by an analysis of resulting conditional entropies.
Unbiased All-Optical Random-Number Generator
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Tobias Steinle
2017-11-01
Full Text Available The generation of random bits is of enormous importance in modern information science. Cryptographic security is based on random numbers which require a physical process for their generation. This is commonly performed by hardware random-number generators. These often exhibit a number of problems, namely experimental bias, memory in the system, and other technical subtleties, which reduce the reliability in the entropy estimation. Further, the generated outcome has to be postprocessed to “iron out” such spurious effects. Here, we present a purely optical randomness generator, based on the bistable output of an optical parametric oscillator. Detector noise plays no role and postprocessing is reduced to a minimum. Upon entering the bistable regime, initially the resulting output phase depends on vacuum fluctuations. Later, the phase is rigidly locked and can be well determined versus a pulse train, which is derived from the pump laser. This delivers an ambiguity-free output, which is reliably detected and associated with a binary outcome. The resulting random bit stream resembles a perfect coin toss and passes all relevant randomness measures. The random nature of the generated binary outcome is furthermore confirmed by an analysis of resulting conditional entropies.
Experimental measurement-device-independent quantum random-number generation
Nie, You-Qi; Guan, Jian-Yu; Zhou, Hongyi; Zhang, Qiang; Ma, Xiongfeng; Zhang, Jun; Pan, Jian-Wei
2016-12-01
The randomness from a quantum random-number generator (QRNG) relies on the accurate characterization of its devices. However, device imperfections and inaccurate characterizations can result in wrong entropy estimation and bias in practice, which highly affects the genuine randomness generation and may even induce the disappearance of quantum randomness in an extreme case. Here we experimentally demonstrate a measurement-device-independent (MDI) QRNG based on time-bin encoding to achieve certified quantum randomness even when the measurement devices are uncharacterized and untrusted. The MDI-QRNG is randomly switched between the regular randomness generation mode and a test mode, in which four quantum states are randomly prepared to perform measurement tomography in real time. With a clock rate of 25 MHz, the MDI-QRNG generates a final random bit rate of 5.7 kbps. Such implementation with an all-fiber setup provides an approach to construct a fully integrated MDI-QRNG with trusted but error-prone devices in practice.
GASPRNG: GPU accelerated scalable parallel random number generator library
Gao, Shuang; Peterson, Gregory D.
2013-04-01
Graphics processors represent a promising technology for accelerating computational science applications. Many computational science applications require fast and scalable random number generation with good statistical properties, so they use the Scalable Parallel Random Number Generators library (SPRNG). We present the GPU Accelerated SPRNG library (GASPRNG) to accelerate SPRNG in GPU-based high performance computing systems. GASPRNG includes code for a host CPU and CUDA code for execution on NVIDIA graphics processing units (GPUs) along with a programming interface to support various usage models for pseudorandom numbers and computational science applications executing on the CPU, GPU, or both. This paper describes the implementation approach used to produce high performance and also describes how to use the programming interface. The programming interface allows a user to be able to use GASPRNG the same way as SPRNG on traditional serial or parallel computers as well as to develop tightly coupled programs executing primarily on the GPU. We also describe how to install GASPRNG and use it. To help illustrate linking with GASPRNG, various demonstration codes are included for the different usage models. GASPRNG on a single GPU shows up to 280x speedup over SPRNG on a single CPU core and is able to scale for larger systems in the same manner as SPRNG. Because GASPRNG generates identical streams of pseudorandom numbers as SPRNG, users can be confident about the quality of GASPRNG for scalable computational science applications. Catalogue identifier: AEOI_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEOI_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licensing provisions: UTK license. No. of lines in distributed program, including test data, etc.: 167900 No. of bytes in distributed program, including test data, etc.: 1422058 Distribution format: tar.gz Programming language: C and CUDA. Computer: Any PC or
A Quickly Tested Pascal Random Number Generator for Microcomputers.
1985-05-01
in any way at equal intervals spaced h units apart, the serial correlation of the series can be obtained for various lags and tested against...pass handily. The unit range between zero and unity was divided into 100 equally spaced frequencies, and the generated random numbers were...NSDTEST; (*MEAN AND SDEV TESTS*) FREQKOLTEST; (*CHISQ FREQ DISTR AND KOLMOGOROFF -SMIRNOV TESTS*) PAIRTEST; (*TEST DISTR OF RANDOM PAIRS*) TRIOTEST; (*TEST
Source-Device-Independent Ultrafast Quantum Random Number Generation
Marangon, Davide G.; Vallone, Giuseppe; Villoresi, Paolo
2017-02-01
Secure random numbers are a fundamental element of many applications in science, statistics, cryptography and more in general in security protocols. We present a method that enables the generation of high-speed unpredictable random numbers from the quadratures of an electromagnetic field without any assumption on the input state. The method allows us to eliminate the numbers that can be predicted due to the presence of classical and quantum side information. In particular, we introduce a procedure to estimate a bound on the conditional min-entropy based on the entropic uncertainty principle for position and momentum observables of infinite dimensional quantum systems. By the above method, we experimentally demonstrated the generation of secure true random bits at a rate greater than 1.7 Gbit /s .
Random Whole Metagenomic Sequencing for Forensic Discrimination of Soils
Khodakova, Anastasia S.; Smith, Renee J.; Burgoyne, Leigh; Abarno, Damien; Linacre, Adrian
2014-01-01
Here we assess the ability of random whole metagenomic sequencing approaches to discriminate between similar soils from two geographically distinct urban sites for application in forensic science. Repeat samples from two parklands in residential areas separated by approximately 3 km were collected and the DNA was extracted. Shotgun, whole genome amplification (WGA) and single arbitrarily primed DNA amplification (AP-PCR) based sequencing techniques were then used to generate soil metagenomic profiles. Full and subsampled metagenomic datasets were then annotated against M5NR/M5RNA (taxonomic classification) and SEED Subsystems (metabolic classification) databases. Further comparative analyses were performed using a number of statistical tools including: hierarchical agglomerative clustering (CLUSTER); similarity profile analysis (SIMPROF); non-metric multidimensional scaling (NMDS); and canonical analysis of principal coordinates (CAP) at all major levels of taxonomic and metabolic classification. Our data showed that shotgun and WGA-based approaches generated highly similar metagenomic profiles for the soil samples such that the soil samples could not be distinguished accurately. An AP-PCR based approach was shown to be successful at obtaining reproducible site-specific metagenomic DNA profiles, which in turn were employed for successful discrimination of visually similar soil samples collected from two different locations. PMID:25111003
Random whole metagenomic sequencing for forensic discrimination of soils.
Directory of Open Access Journals (Sweden)
Anastasia S Khodakova
Full Text Available Here we assess the ability of random whole metagenomic sequencing approaches to discriminate between similar soils from two geographically distinct urban sites for application in forensic science. Repeat samples from two parklands in residential areas separated by approximately 3 km were collected and the DNA was extracted. Shotgun, whole genome amplification (WGA and single arbitrarily primed DNA amplification (AP-PCR based sequencing techniques were then used to generate soil metagenomic profiles. Full and subsampled metagenomic datasets were then annotated against M5NR/M5RNA (taxonomic classification and SEED Subsystems (metabolic classification databases. Further comparative analyses were performed using a number of statistical tools including: hierarchical agglomerative clustering (CLUSTER; similarity profile analysis (SIMPROF; non-metric multidimensional scaling (NMDS; and canonical analysis of principal coordinates (CAP at all major levels of taxonomic and metabolic classification. Our data showed that shotgun and WGA-based approaches generated highly similar metagenomic profiles for the soil samples such that the soil samples could not be distinguished accurately. An AP-PCR based approach was shown to be successful at obtaining reproducible site-specific metagenomic DNA profiles, which in turn were employed for successful discrimination of visually similar soil samples collected from two different locations.
Compact quantum random number generator based on superluminescent light-emitting diodes
Wei, Shihai; Yang, Jie; Fan, Fan; Huang, Wei; Li, Dashuang; Xu, Bingjie
2017-12-01
By measuring the amplified spontaneous emission (ASE) noise of the superluminescent light emitting diodes, we propose and realize a quantum random number generator (QRNG) featured with practicability. In the QRNG, after the detection and amplification of the ASE noise, the data acquisition and randomness extraction which is integrated in a field programmable gate array (FPGA) are both implemented in real-time, and the final random bit sequences are delivered to a host computer with a real-time generation rate of 1.2 Gbps. Further, to achieve compactness, all the components of the QRNG are integrated on three independent printed circuit boards with a compact design, and the QRNG is packed in a small enclosure sized 140 mm × 120 mm × 25 mm. The final random bit sequences can pass all the NIST-STS and DIEHARD tests.
Quantum random number generator based on quantum nature of vacuum fluctuations
Ivanova, A. E.; Chivilikhin, S. A.; Gleim, A. V.
2017-11-01
Quantum random number generator (QRNG) allows obtaining true random bit sequences. In QRNG based on quantum nature of vacuum, optical beam splitter with two inputs and two outputs is normally used. We compare mathematical descriptions of spatial beam splitter and fiber Y-splitter in the quantum model for QRNG, based on homodyne detection. These descriptions were identical, that allows to use fiber Y-splitters in practical QRNG schemes, simplifying the setup. Also we receive relations between the input radiation and the resulting differential current in homodyne detector. We experimentally demonstrate possibility of true random bits generation by using QRNG based on homodyne detection with Y-splitter.
The Evolution of Random Number Generation in MUVES
2017-01-01
3 2. Collins JC . Testing, selection, and implementation of random number genera- tors. Aberdeen Proving Ground (MD): Army Research Laboratory (US...261–269. 13, 16 5. L‘Ecuyer P. Tables of linear congruential generators of different sizes and good lattice structure. Mathematics of Computation
A random-matrix theory of the number sense.
Hannagan, T; Nieder, A; Viswanathan, P; Dehaene, S
2017-02-19
Number sense, a spontaneous ability to process approximate numbers, has been documented in human adults, infants and newborns, and many other animals. Species as distant as monkeys and crows exhibit very similar neurons tuned to specific numerosities. How number sense can emerge in the absence of learning or fine tuning is currently unknown. We introduce a random-matrix theory of self-organized neural states where numbers are coded by vectors of activation across multiple units, and where the vector codes for successive integers are obtained through multiplication by a fixed but random matrix. This cortical implementation of the 'von Mises' algorithm explains many otherwise disconnected observations ranging from neural tuning curves in monkeys to looking times in neonates and cortical numerotopy in adults. The theory clarifies the origin of Weber-Fechner's Law and yields a novel and empirically validated prediction of multi-peak number neurons. Random matrices constitute a novel mechanism for the emergence of brain states coding for quantity.This article is part of a discussion meeting issue 'The origins of numerical abilities'. © 2017 The Author(s).
The Total Acquisition Number Of The Randomly Weighted Path
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Godbole Anant
2017-11-01
Full Text Available There exists a significant body of work on determining the acquisition number at(G of various graphs when the vertices of those graphs are each initially assigned a unit weight. We determine properties of the acquisition number of the path, star, complete, complete bipartite, cycle, and wheel graphs for variations on this initial weighting scheme, with the majority of our work focusing on the expected acquisition number of randomly weighted graphs. In particular, we bound the expected acquisition number E(at(Pn of the n-path when n distinguishable “units” of integral weight, or chips, are randomly distributed across its vertices between 0.242n and 0.375n. With computer support, we improve it by showing that E(at(Pn lies between 0.29523n and 0.29576n. We then use subadditivity to show that the limiting ratio lim E(at(Pn/n exists, and simulations reveal more exactly what the limiting value equals. The Hoeffding-Azuma inequality is used to prove that the acquisition number is tightly concentrated around its expected value. Additionally, in a different context, we offer a non-optimal acquisition protocol algorithm for the randomly weighted path and exactly compute the expected size of the resultant residual set.
An On-Demand Optical Quantum Random Number Generator with In-Future Action and Ultra-Fast Response.
Stipčević, Mario; Ursin, Rupert
2015-06-09
Random numbers are essential for our modern information based society e.g. in cryptography. Unlike frequently used pseudo-random generators, physical random number generators do not depend on complex algorithms but rather on a physical process to provide true randomness. Quantum random number generators (QRNG) do rely on a process, which can be described by a probabilistic theory only, even in principle. Here we present a conceptually simple implementation, which offers a 100% efficiency of producing a random bit upon a request and simultaneously exhibits an ultra low latency. A careful technical and statistical analysis demonstrates its robustness against imperfections of the actual implemented technology and enables to quickly estimate randomness of very long sequences. Generated random numbers pass standard statistical tests without any post-processing. The setup described, as well as the theory presented here, demonstrate the maturity and overall understanding of the technology.
Entropy and long-range correlations in random symbolic sequences
Melnik, S S
2014-01-01
The goal of this paper is to develop an estimate for the entropy of random long-range correlated symbolic sequences with elements belonging to a finite alphabet. As a plausible model, we use the high-order additive stationary ergodic Markov chain. Supposing that the correlations between random elements of the chain are weak we express the differential entropy of the sequence by means of the symbolic pair correlation function. We also examine an algorithm for estimating the differential entropy of finite symbolic sequences. We show that the entropy contains two contributions, the correlation and fluctuation ones. The obtained analytical results are used for numerical evaluation of the entropy of written English texts and DNA nucleotide sequences. The developed theory opens the way for constructing a more consistent and sophisticated approach to describe the systems with strong short- and weak long-range correlations.
p-Absolutely summable sequences of fuzzy real numbers
Directory of Open Access Journals (Sweden)
Ayhan Esi
2013-03-01
Full Text Available In this paper the fuzzy sequence space is introduced and some algebraic properties such as solidness, symmetricalness, convergence free and sequence algebra are studied, and some inclusion relations for the space are provided.
Solution-Processed Carbon Nanotube True Random Number Generator.
Gaviria Rojas, William A; McMorrow, Julian J; Geier, Michael L; Tang, Qianying; Kim, Chris H; Marks, Tobin J; Hersam, Mark C
2017-08-09
With the growing adoption of interconnected electronic devices in consumer and industrial applications, there is an increasing demand for robust security protocols when transmitting and receiving sensitive data. Toward this end, hardware true random number generators (TRNGs), commonly used to create encryption keys, offer significant advantages over software pseudorandom number generators. However, the vast network of devices and sensors envisioned for the "Internet of Things" will require small, low-cost, and mechanically flexible TRNGs with low computational complexity. These rigorous constraints position solution-processed semiconducting single-walled carbon nanotubes (SWCNTs) as leading candidates for next-generation security devices. Here, we demonstrate the first TRNG using static random access memory (SRAM) cells based on solution-processed SWCNTs that digitize thermal noise to generate random bits. This bit generation strategy can be readily implemented in hardware with minimal transistor and computational overhead, resulting in an output stream that passes standardized statistical tests for randomness. By using solution-processed semiconducting SWCNTs in a low-power, complementary architecture to achieve TRNG, we demonstrate a promising approach for improving the security of printable and flexible electronics.
Chaos-based Pseudo-random Number Generation
Barakat, Mohamed L.
2014-04-10
Various methods and systems related to chaos-based pseudo-random number generation are presented. In one example, among others, a system includes a pseudo-random number generator (PRNG) to generate a series of digital outputs and a nonlinear post processing circuit to perform an exclusive OR (XOR) operation on a first portion of a current digital output of the PRNG and a permutated version of a corresponding first portion of a previous post processed output to generate a corresponding first portion of a current post processed output. In another example, a method includes receiving at least a first portion of a current output from a PRNG and performing an XOR operation on the first portion of the current PRNG output with a permutated version of a corresponding first portion of a previous post processed output to generate a corresponding first portion of a current post processed output.
Miszczak, Jarosław Adam
2013-01-01
The presented package for the Mathematica computing system allows the harnessing of quantum random number generators (QRNG) for investigating the statistical properties of quantum states. The described package implements a number of functions for generating random states. The new version of the package adds the ability to use the on-line quantum random number generator service and implements new functions for retrieving lists of random numbers. Thanks to the introduced improvements, the new version provides faster access to high-quality sources of random numbers and can be used in simulations requiring large amount of random data. New version program summaryProgram title: TRQS Catalogue identifier: AEKA_v2_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEKA_v2_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 18 134 No. of bytes in distributed program, including test data, etc.: 2 520 49 Distribution format: tar.gz Programming language: Mathematica, C. Computer: Any supporting Mathematica in version 7 or higher. Operating system: Any platform supporting Mathematica; tested with GNU/Linux (32 and 64 bit). RAM: Case-dependent Supplementary material: Fig. 1 mentioned below can be downloaded. Classification: 4.15. External routines: Quantis software library (http://www.idquantique.com/support/quantis-trng.html) Catalogue identifier of previous version: AEKA_v1_0 Journal reference of previous version: Comput. Phys. Comm. 183(2012)118 Does the new version supersede the previous version?: Yes Nature of problem: Generation of random density matrices and utilization of high-quality random numbers for the purpose of computer simulation. Solution method: Use of a physical quantum random number generator and an on-line service providing access to the source of true random
Classification of periodic, chaotic and random sequences using ...
Indian Academy of Sciences (India)
ities of different datasets. Entropy cannot differentiate between chaotic and random sequences while ApEn and LZ cannot distinguish between weak and strong chaos. Figure 1. 95% confidence interval for mean LZ complexity of 50 samples of length. 20 using four bins. Pramana – J. Phys., Vol. 84, No. 3, March 2015. 367 ...
Energy Technology Data Exchange (ETDEWEB)
Stipčević, Mario, E-mail: mario.stipcevic@irb.hr [Photonics and Quantum Optics Research Unit, Center of Excellence for Advanced Materials and Sensing Devices, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb (Croatia)
2016-03-15
In this work, a new type of elementary logic circuit, named random flip-flop (RFF), is proposed, experimentally realized, and studied. Unlike conventional Boolean logic circuits whose action is deterministic and highly reproducible, the action of a RFF is intentionally made maximally unpredictable and, in the proposed realization, derived from a fundamentally random process of emission and detection of light quanta. We demonstrate novel applications of RFF in randomness preserving frequency division, random frequency synthesis, and random number generation. Possible usages of these applications in the information and communication technology, cryptographic hardware, and testing equipment are discussed.
Prediction of Protein Hotspots from Whole Protein Sequences by a Random Projection Ensemble System
Directory of Open Access Journals (Sweden)
Jinjian Jiang
2017-07-01
Full Text Available Hotspot residues are important in the determination of protein-protein interactions, and they always perform specific functions in biological processes. The determination of hotspot residues is by the commonly-used method of alanine scanning mutagenesis experiments, which is always costly and time consuming. To address this issue, computational methods have been developed. Most of them are structure based, i.e., using the information of solved protein structures. However, the number of solved protein structures is extremely less than that of sequences. Moreover, almost all of the predictors identified hotspots from the interfaces of protein complexes, seldom from the whole protein sequences. Therefore, determining hotspots from whole protein sequences by sequence information alone is urgent. To address the issue of hotspot predictions from the whole sequences of proteins, we proposed an ensemble system with random projections using statistical physicochemical properties of amino acids. First, an encoding scheme involving sequence profiles of residues and physicochemical properties from the AAindex1 dataset is developed. Then, the random projection technique was adopted to project the encoding instances into a reduced space. Then, several better random projections were obtained by training an IBk classifier based on the training dataset, which were thus applied to the test dataset. The ensemble of random projection classifiers is therefore obtained. Experimental results showed that although the performance of our method is not good enough for real applications of hotspots, it is very promising in the determination of hotspot residues from whole sequences.
Prediction of Protein Hotspots from Whole Protein Sequences by a Random Projection Ensemble System
Jiang, Jinjian; Wang, Nian; Chen, Peng; Zheng, Chunhou; Wang, Bing
2017-01-01
Hotspot residues are important in the determination of protein-protein interactions, and they always perform specific functions in biological processes. The determination of hotspot residues is by the commonly-used method of alanine scanning mutagenesis experiments, which is always costly and time consuming. To address this issue, computational methods have been developed. Most of them are structure based, i.e., using the information of solved protein structures. However, the number of solved protein structures is extremely less than that of sequences. Moreover, almost all of the predictors identified hotspots from the interfaces of protein complexes, seldom from the whole protein sequences. Therefore, determining hotspots from whole protein sequences by sequence information alone is urgent. To address the issue of hotspot predictions from the whole sequences of proteins, we proposed an ensemble system with random projections using statistical physicochemical properties of amino acids. First, an encoding scheme involving sequence profiles of residues and physicochemical properties from the AAindex1 dataset is developed. Then, the random projection technique was adopted to project the encoding instances into a reduced space. Then, several better random projections were obtained by training an IBk classifier based on the training dataset, which were thus applied to the test dataset. The ensemble of random projection classifiers is therefore obtained. Experimental results showed that although the performance of our method is not good enough for real applications of hotspots, it is very promising in the determination of hotspot residues from whole sequences. PMID:28718782
Computer routines for probability distributions, random numbers, and related functions
Kirby, W.
1983-01-01
Use of previously coded and tested subroutines simplifies and speeds up program development and testing. This report presents routines that can be used to calculate various probability distributions and other functions of importance in statistical hydrology. The routines are designed as general-purpose Fortran subroutines and functions to be called from user-written main progress. The probability distributions provided include the beta, chi-square, gamma, Gaussian (normal), Pearson Type III (tables and approximation), and Weibull. Also provided are the distributions of the Grubbs-Beck outlier test, Kolmogorov 's and Smirnov 's D, Student 's t, noncentral t (approximate), and Snedecor F. Other mathematical functions include the Bessel function, I sub o, gamma and log-gamma functions, error functions, and exponential integral. Auxiliary services include sorting and printer-plotting. Random number generators for uniform and normal numbers are provided and may be used with some of the above routines to generate numbers from other distributions. (USGS)
640-Gbit/s fast physical random number generation using a broadband chaotic semiconductor laser
Zhang, Limeng; Pan, Biwei; Chen, Guangcan; Guo, Lu; Lu, Dan; Zhao, Lingjuan; Wang, Wei
2017-04-01
An ultra-fast physical random number generator is demonstrated utilizing a photonic integrated device based broadband chaotic source with a simple post data processing method. The compact chaotic source is implemented by using a monolithic integrated dual-mode amplified feedback laser (AFL) with self-injection, where a robust chaotic signal with RF frequency coverage of above 50 GHz and flatness of ±3.6 dB is generated. By using 4-least significant bits (LSBs) retaining from the 8-bit digitization of the chaotic waveform, random sequences with a bit-rate up to 640 Gbit/s (160 GS/s × 4 bits) are realized. The generated random bits have passed each of the fifteen NIST statistics tests (NIST SP800-22), indicating its randomness for practical applications.
Random number generation based on digital differential chaos
Zidan, Mohammed A.
2012-07-29
In this paper, we present a fully digital differential chaos based random number generator. The output of the digital circuit is proved to be chaotic by calculating the output time series maximum Lyapunov exponent. We introduce a new post processing technique to improve the distribution and statistical properties of the generated data. The post-processed output passes the NIST Sp. 800-22 statistical tests. The system is written in Verilog VHDL and realized on Xilinx Virtex® FPGA. The generator can fit into a very small area and have a maximum throughput of 2.1 Gb/s.
Quantum Statistical Testing of a Quantum Random Number Generator
Energy Technology Data Exchange (ETDEWEB)
Humble, Travis S [ORNL
2014-01-01
The unobservable elements in a quantum technology, e.g., the quantum state, complicate system verification against promised behavior. Using model-based system engineering, we present methods for verifying the opera- tion of a prototypical quantum random number generator. We begin with the algorithmic design of the QRNG followed by the synthesis of its physical design requirements. We next discuss how quantum statistical testing can be used to verify device behavior as well as detect device bias. We conclude by highlighting how system design and verification methods must influence effort to certify future quantum technologies.
Lockwood, M.; Owens, M. J.; Barnard, L.
2016-11-01
We use five test data series to search for, and quantify, putative discontinuities around 1946 in five different annual-mean sunspot-number or sunspot-group-number data sequences. The data series tested are the original and new versions of the Wolf/Zürich/International sunspot number composite [R_{{ISNv1}} and R_{{ISNv2}}] (respectively Clette et al. in Adv. Space Res. 40, 919, 2007 and Clette et al. in The Solar Activity Cycle 35, Springer, New York, 2015); the corrected version of R ISNv1 proposed by Lockwood, Owens, and Barnard ( J. Geophys. Res. 119, 5193, 2014a) [R C]; the new "backbone" group-number composite proposed by Svalgaard and Schatten ( Solar Phys. 291, 2016) [R_{{BB}}]; and the new group-number composite derived by Usoskin et al. ( Solar Phys. 291, 2016) [R_{{UEA}}]. The test data series used are the group-number [NG] and total sunspot area [A G] from the Royal Observatory, Greenwich/Royal Greenwich Observatory (RGO) photoheliographic data; the Ca K index from the recent re-analysis of Mount Wilson Observatory (MWO) spectroheliograms in the Calcium ii K ion line; the sunspot-group-number from the MWO sunspot drawings [N_{{MWO}}]; and the dayside ionospheric F2-region critical frequencies measured by the Slough ionosonde [foF2]. These test data all vary in close association with sunspot numbers, in some cases non-linearly. The tests are carried out using both the before-and-after fit-residual comparison method and the correlation method of Lockwood, Owens, and Barnard, applied to annual mean data for intervals iterated to minimise errors and to eliminate uncertainties associated with the precise date of the putative discontinuity. It is not assumed that the correction required is by a constant factor, nor even linear in sunspot number. It is shown that a non-linear correction is required by RC, R_{BB}, and R_{{ISNv1}}, but not by R_{{ISNv2}} or R_{{UEA}}. The five test datasets give very similar results in all cases. By multiplying the probability
Balygin, K. A.; Zaitsev, V. I.; Klimov, A. N.; Kulik, S. P.; Molotkov, S. N.; Popova, E.; Vinogradov, S.
2017-12-01
We implemented experimentally a quantum random number generator, based on the registration of quasi-single-photon light by a silicon photo-multiplier, which allows one to reliably achieve the Poisson statistics of photocounts. The use of the optimal grouping of photocounts and a polynomial-length sequence of the method for extracting the random sequence 0 and 1 made it possible to achieve the output rate of a provably random sequence up to 75 Mbit s-1 .
Fully Digital Chaotic Oscillators Applied to Pseudo Random Number Generation
Mansingka, Abhinav S.
2012-05-01
adapted for pseudo random number generation by truncating statistically defective bits. Finally, a novel post-processing technique using the Fibonacci series is proposed and implemented with a non-autonomous driven hyperchaotic system to provide pseudo random number generators with high nonlinear complexity and controllable period length that enables full utilization of all branches of the chaotic output as statistically secure pseudo random output.
Directory of Open Access Journals (Sweden)
Davide De Lucrezia
Full Text Available Are extant proteins the exquisite result of natural selection or are they random sequences slightly edited by evolution? This question has puzzled biochemists for long time and several groups have addressed this issue comparing natural protein sequences to completely random ones coming to contradicting conclusions. Previous works in literature focused on the analysis of primary structure in an attempt to identify possible signature of evolutionary editing. Conversely, in this work we compare a set of 762 natural proteins with an average length of 70 amino acids and an equal number of completely random ones of comparable length on the basis of their structural features. We use an ad hoc Evolutionary Neural Network Algorithm (ENNA in order to assess whether and to what extent natural proteins are edited from random polypeptides employing 11 different structure-related variables (i.e. net charge, volume, surface area, coil, alpha helix, beta sheet, percentage of coil, percentage of alpha helix, percentage of beta sheet, percentage of secondary structure and surface hydrophobicity. The ENNA algorithm is capable to correctly distinguish natural proteins from random ones with an accuracy of 94.36%. Furthermore, we study the structural features of 32 random polypeptides misclassified as natural ones to unveil any structural similarity to natural proteins. Results show that random proteins misclassified by the ENNA algorithm exhibit a significant fold similarity to portions or subdomains of extant proteins at atomic resolution. Altogether, our results suggest that natural proteins are significantly edited from random polypeptides and evolutionary editing can be readily detected analyzing structural features. Furthermore, we also show that the ENNA, employing simple structural descriptors, can predict whether a protein chain is natural or random.
Generative Learning Objects Instantiated with Random Numbers Based Expressions
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Ciprian Bogdan Chirila
2015-12-01
Full Text Available The development of interactive e-learning content requires special skills like programming techniques, web integration, graphic design etc. Generally, online educators do not possess such skills and their e-learning products tend to be static like presentation slides and textbooks. In this paper we propose a new interactive model of generative learning objects as a compromise betweenstatic, dull materials and dynamic, complex software e-learning materials developed by specialized teams. We find that random numbers based automatic initialization learning objects increases content diversity, interactivity thus enabling learners’ engagement. The resulted learning object model is at a limited level of complexity related to special e-learning software, intuitive and capable of increasing learners’ interactivity, engagement and motivation through dynamic content. The approach was applied successfully on several computer programing disciplines.
Peptide based diagnostics: are random-sequence peptides more useful than tiling proteome sequences?
Navalkar, Krupa Arun; Johnston, Stephan Albert; Stafford, Phillip
2015-02-01
Diagnostics using peptide ligands have been available for decades. However, their adoption in diagnostics has been limited, not because of poor sensitivity but in many cases due to diminished specificity. Numerous reports suggest that protein-based rather than peptide-based disease detection is more specific. We examined two different approaches to peptide-based diagnostics using Coccidioides (aka Valley Fever) as the disease model. Although the pathogen was discovered more than a century ago, a highly sensitive diagnostic remains unavailable. We present a case study where two different approaches to diagnosing Valley Fever were used: first, overlapping Valley Fever epitopes representing immunodominant Coccidioides antigens were tiled using a microarray format of presynthesized peptides. Second, a set of random sequence peptides identified using a 10,000 peptide immunosignaturing microarray was compared for sensitivity and specificity. The scientific hypothesis tested was that actual epitope peptides from Coccidioides would provide sufficient sensitivity and specificity as a diagnostic. Results demonstrated that random sequence peptides exhibited higher accuracy when classifying different stages of Valley Fever infection vs. epitope peptides. The epitope peptide array did provide better performance than the existing immunodiffusion array, but when directly compared to the random sequence peptides, reported lower overall accuracy. This study suggests that there are competing aspects of antibody recognition that involve conservation of pathogen sequence and aspects of mimotope recognition and amino acid substitutions. These factors may prove critical when developing the next generation of high-performance immunodiagnostics. Copyright © 2014 Elsevier B.V. All rights reserved.
Inter simple sequence repeats (ISSR) and random amplified ...
African Journals Online (AJOL)
21 of 30 random amplified polymorphic DNA (RAPD) primers produced 220 reproducible bands with average of 10.47 bands per primer and 80.12% of polymorphism. OPR02 primer showed the highest number of effective allele (Ne), Shannon index (I) and genetic diversity (H). Some of the cultivars had specific bands, ...
A revision of the subtract-with-borrow random number generators
Sibidanov, Alexei
2017-12-01
The most popular and widely used subtract-with-borrow generator, also known as RANLUX, is reimplemented as a linear congruential generator using large integer arithmetic with the modulus size of 576 bits. Modern computers, as well as the specific structure of the modulus inferred from RANLUX, allow for the development of a fast modular multiplication - the core of the procedure. This was previously believed to be slow and have too high cost in terms of computing resources. Our tests show a significant gain in generation speed which is comparable with other fast, high quality random number generators. An additional feature is the fast skipping of generator states leading to a seeding scheme which guarantees the uniqueness of random number sequences. Licensing provisions: GPLv3 Programming language: C++, C, Assembler
Random-breakage mapping method applied to human DNA sequences
Lobrich, M.; Rydberg, B.; Cooper, P. K.; Chatterjee, A. (Principal Investigator)
1996-01-01
The random-breakage mapping method [Game et al. (1990) Nucleic Acids Res., 18, 4453-4461] was applied to DNA sequences in human fibroblasts. The methodology involves NotI restriction endonuclease digestion of DNA from irradiated calls, followed by pulsed-field gel electrophoresis, Southern blotting and hybridization with DNA probes recognizing the single copy sequences of interest. The Southern blots show a band for the unbroken restriction fragments and a smear below this band due to radiation induced random breaks. This smear pattern contains two discontinuities in intensity at positions that correspond to the distance of the hybridization site to each end of the restriction fragment. By analyzing the positions of those discontinuities we confirmed the previously mapped position of the probe DXS1327 within a NotI fragment on the X chromosome, thus demonstrating the validity of the technique. We were also able to position the probes D21S1 and D21S15 with respect to the ends of their corresponding NotI fragments on chromosome 21. A third chromosome 21 probe, D21S11, has previously been reported to be close to D21S1, although an uncertainty about a second possible location existed. Since both probes D21S1 and D21S11 hybridized to a single NotI fragment and yielded a similar smear pattern, this uncertainty is removed by the random-breakage mapping method.
Ghersi, Dario; Parakh, Abhishek; Mezei, Mihaly
2017-12-05
Four pseudorandom number generators were compared with a physical, quantum-based random number generator using the NIST suite of statistical tests, which only the quantum-based random number generator could successfully pass. We then measured the effect of the five random number generators on various calculated properties in different Markov-chain Monte Carlo simulations. Two types of systems were tested: conformational sampling of a small molecule in aqueous solution and liquid methanol under constant temperature and pressure. The results show that poor quality pseudorandom number generators produce results that deviate significantly from those obtained with the quantum-based random number generator, particularly in the case of the small molecule in aqueous solution setup. In contrast, the widely used Mersenne Twister pseudorandom generator and a 64-bit Linear Congruential Generator with a scrambler produce results that are statistically indistinguishable from those obtained with the quantum-based random number generator. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Some Double Sequence Spaces of Fuzzy Real Numbers of Paranormed Type
Directory of Open Access Journals (Sweden)
Bipul Sarma
2013-01-01
Full Text Available We study different properties of convergent, null, and bounded double sequence spaces of fuzzy real numbers like completeness, solidness, sequence algebra, symmetricity, convergence-free, and so forth. We prove some inclusion results too.
rMotifGen: random motif generator for DNA and protein sequences
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Hardin C Timothy
2007-08-01
Full Text Available Abstract Background Detection of short, subtle conserved motif regions within a set of related DNA or amino acid sequences can lead to discoveries about important regulatory domains such as transcription factor and DNA binding sites as well as conserved protein domains. In order to help assess motif detection algorithms on motifs with varying properties and levels of conservation, we have developed a computational tool, rMotifGen, with the sole purpose of generating a number of random DNA or protein sequences containing short sequence motifs. Each motif consensus can be user-defined, randomly generated, or created from a position-specific scoring matrix (PSSM. Insertions and mutations within these motifs are created according to user-defined parameters and substitution matrices. The resulting sequences can be helpful in mutational simulations and in testing the limits of motif detection algorithms. Results Two implementations of rMotifGen have been created, one providing a graphical user interface (GUI for random motif construction, and the other serving as a command line interface. The second implementation has the added advantages of platform independence and being able to be called in a batch mode. rMotifGen was used to construct sample sets of sequences containing DNA motifs and amino acid motifs that were then tested against the Gibbs sampler and MEME packages. Conclusion rMotifGen provides an efficient and convenient method for creating random DNA or amino acid sequences with a variable number of motifs, where the instance of each motif can be incorporated using a position-specific scoring matrix (PSSM or by creating an instance mutated from its corresponding consensus using an evolutionary model based on substitution matrices. rMotifGen is freely available at: http://bioinformatics.louisville.edu/brg/rMotifGen/.
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Bilan Stepan
2017-01-01
Full Text Available To date, there are many tasks that are aimed at studying the dynamic changes in physical processes. These tasks do not give advance known result. The solution of such problems is based on the construction of a dynamic model of the object. Successful structural and functional implementation of the object model can give a positive result in time. This approach uses the task of constructing artificial biological objects. To solve such problems, pseudo-random number generators are used, which also find wide application for information protection tasks. Such generators should have good statistical properties and give a long repetition period of the generated pseudo-random bit sequence. This work is aimed at improving these characteristics. The paper considers the method of forming pseudo-random sequences of numbers on the basis of aperiodic cellular automata with two active cells. A pseudo-random number generator is proposed that generates three bit sequences. The first two bit sequences are formed by the corresponding two active cells in the cellular automaton. The third bit sequence is the result of executing the XOR function over the bits of the first two sequences and it has better characteristics compared to them. The use of cellular automata with two active cells allowed to improve the statistical properties of the formed bit sequence, as well as its repetition period. This is proved by using graphical tests for generators built based on cellular automata using the neighborhoods of von Neumann and Moore. The tests showed high efficiency of the generator based on an asynchronous cellular automaton with the neighborhood of Moore. The proposed pseudo-random number generators have good statistical properties, which makes it possible to use them in information security systems, as well as for simulation tasks of various dynamic processes.
PRIMITIVE MATRICES AND GENERATORS OF PSEUDO RANDOM SEQUENCES OF GALOIS
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A. Beletsky
2014-04-01
Full Text Available In theory and practice of information cryptographic protection one of the key problems is the forming a binary pseudo-random sequences (PRS with a maximum length with acceptable statistical characteristics. PRS generators are usually implemented by linear shift register (LSR of maximum period with linear feedback [1]. In this paper we extend the concept of LSR, assuming that each of its rank (memory cell can be in one of the following condition. Let’s call such registers “generalized linear shift register.” The research goal is to develop algorithms for constructing Galois and Fibonacci generalized matrix of n-order over the field , which uniquely determined both the structure of corresponding generalized of n-order LSR maximal period, and formed on their basis Galois PRS generators of maximum length. Thus the article presents the questions of formation the primitive generalized Fibonacci and Galois arbitrary order matrix over the prime field . The synthesis of matrices is based on the use of irreducible polynomials of degree and primitive elements of the extended field generated by polynomial. The constructing methods of Galois and Fibonacci conjugated primitive matrices are suggested. The using possibilities of such matrices in solving the problem of constructing generalized generators of Galois pseudo-random sequences are discussed.
Some Classes of Difference Sequence Spaces of Fuzzy Real Numbers Defined by Orlicz Function
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Binod Chandra Tripathy
2011-01-01
Full Text Available We introduce the classes of generalized difference bounded, convergent, and null sequences of fuzzy real numbers defined by an Orlicz function. Some properties of these sequence spaces like solidness, symmetricity, and convergence-free are studied. We obtain some inclusion relations involving these sequence spaces.
$\\mathcal{I}$ and $\\mathcal{I}^{\\ast}$ convergence of multiple sequences of fuzzy numbers
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Pankaj Kumar
2015-07-01
Full Text Available Recently, the concept of statistical convergence for multiple sequences of fuzzy numbers has been studied by Kumar et al. This motivate us to extend the idea of $\\mathcal{I}$-convergence to sequences of fuzzy numbers of multiplicity greater than two.
RefCNV: Identification of Gene-Based Copy Number Variants Using Whole Exome Sequencing
Lun-Ching Chang; Biswajit Das; Chih-Jian Lih; Han Si; Camalier, Corinne E.; Paul M. McGregor III; Eric Polley
2016-01-01
With rapid advances in DNA sequencing technologies, whole exome sequencing (WES) has become a popular approach for detecting somatic mutations in oncology studies. The initial intent of WES was to characterize single nucleotide variants, but it was observed that the number of sequencing reads that mapped to a genomic region correlated with the DNA copy number variants (CNVs). We propose a method RefCNV that uses a reference set to estimate the distribution of the coverage for each exon. The c...
On some generalised I-convergent sequence spaces of double interval numbers
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Esi Esi
2016-04-01
Full Text Available In this article we introduce and study some spaces of I-convergent sequences of double interval numbers with the help of a double sequence F=(f_{i,j} of modulii and double bounded sequence p=(p_{i,j} of positive real numbers. We study some topological and algebraic properties, prove the decomposition theorem and study some inclusion relations on these spaces.
A note on the strong law of large numbers for associated sequences
Directory of Open Access Journals (Sweden)
A. Nezakati
2005-01-01
Full Text Available We prove that the sequence {bn−1∑i=1n(Xi−EXi}n≥1 converges a.e. to zero if {Xn,n≥1} is anassociated sequence of random variables with ∑n=1∞bkn−2Var(∑i=kn−1+1knXi<∞ where {bn,n≥1} is a positive nondecreasing sequence and {kn,n≥1} is a strictly increasing sequence, both tending to infinity as n tends to infinity and 0
Framework for testing random numbers in parallel calculations
DEFF Research Database (Denmark)
Vattulainen, Ilpo Tapio
1999-01-01
sequence. The asymptotic power-law behavior of the corresponding correlation functions yields exponents, which can be compared with exact theoretical results. Correlations prior to the asymptotic regime can be further investigated by other complementary methods. We demonstrate this approach by three...
A generator for unique quantum random numbers based on vacuum states
DEFF Research Database (Denmark)
Gabriel, C.; Wittmann, C.; Sych, D.
2010-01-01
Random numbers are a valuable component in diverse applications that range from simulations(1) over gambling to cryptography(2,3). The quest for true randomness in these applications has engendered a large variety of different proposals for producing random numbers based on the foundational unpre...
Effective Normalization for Copy Number Variation Detection from Whole Genome Sequencing
Janevski, A.; Varadan, V.; Kamalakaran, S.; Banerjee, N.; Dimitrova, D.
2012-01-01
Background Whole genome sequencing enables a high resolution view ofthe human genome and provides unique insights into genome structureat an unprecedented scale. There have been a number of tools to infer copy number variation in the genome. These tools while validatedalso include a number of
EXCAVATOR: detecting copy number variants from whole-exome sequencing data
National Research Council Canada - National Science Library
Magi, Alberto; Tattini, Lorenzo; Cifola, Ingrid; D'Aurizio, Romina; Benelli, Matteo; Mangano, Eleonora; Battaglia, Cristina; Bonora, Elena; Kurg, Ants; Seri, Marco; Magini, Pamela; Giusti, Betti; Romeo, Giovanni; Pippucci, Tommaso; De Bellis, Gianluca; Abbate, Rosanna; Gensini, Gian Franco
2013-01-01
...) from whole-exome sequencing data. EXCAVATOR combines a three-step normalization procedure with a novel heterogeneous hidden Markov model algorithm and a calling method that classifies genomic regions into five copy number states...
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Mingle Guo
2012-01-01
Full Text Available The complete convergence for weighted sums of sequences of negatively dependent random variables is investigated. By applying moment inequality and truncation methods, the equivalent conditions of complete convergence for weighted sums of sequences of negatively dependent random variables are established. These results not only extend the corresponding results obtained by Li et al. (1995, Gut (1993, and Liang (2000 to sequences of negatively dependent random variables, but also improve them.
High-Quality Random Number Generation Software for High-Performance Computing Project
National Aeronautics and Space Administration — Random number (RN) generation is the key software component that permits random sampling. Software for parallel RN generation (RNG) should be based on RNGs that are...
Investigating Triangular Numbers with greatest integer function, Sequences and Double Factorial
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Tilahun A Muche
2016-11-01
Full Text Available The Triangular number denoted by is defined as the sum of the first consecutive positive integers. A positive integer is a Triangular Number if and only if [1]. We stated and proved a sequence of positive integers is consecutive triangular numbers if and only if √ − √ =1 and √ . We consider a ceiling function ⌈ ⌉ to state and prove a necessary and sufficient condition for a number ⌈ ⌉ ⌈ ⌉ to be a triangular number for each . A formula to find and of any two consecutive triangular numbers and a double factorial is introduced to find products of triangular numbers.
Design of Long Period Pseudo-Random Sequences from the Addition of m -Sequences over 𝔽 p
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Ren Jian
2004-01-01
Full Text Available Pseudo-random sequence with good correlation property and large linear span is widely used in code division multiple access (CDMA communication systems and cryptology for reliable and secure information transmission. In this paper, sequences with long period, large complexity, balance statistics, and low cross-correlation property are constructed from the addition of m -sequences with pairwise-prime linear spans (AMPLS. Using m -sequences as building blocks, the proposed method proved to be an efficient and flexible approach to construct long period pseudo-random sequences with desirable properties from short period sequences. Applying the proposed method to 𝔽 2 , a signal set ( ( 2 n − 1 ( 2 m − 1 , ( 2 n + 1 ( 2 m + 1 , ( 2 ( n + 1 / 2 + 1 ( 2 ( m + 1 / 2 + 1 is constructed.
Impact of random numbers on parallel Monte Carlo application
Energy Technology Data Exchange (ETDEWEB)
Pandey, Ras B.
2002-10-22
A number of graduate students are involved at various level of research in this project. We investigate the basic issues in materials using Monte Carlo simulations with specific interest in heterogeneous materials. Attempts have been made to seek collaborations with the DOE laboratories. Specific details are given.
Individualized cattle copy number and segmental duplication maps using next generation sequencing
Copy Number Variations (CNVs) affect a wide range of phenotypic traits; however, CNVs in or near segmental duplication regions are often intractable. Using a read depth approach based on next generation sequencing, we examined genome-wide copy number differences among five taurine (three Angus, one ...
Copy number variation of individual cattle genomes using next-generation sequencing
Copy number variations (CNVs) affect a wide range of phenotypic traits; however, CNVs in or near segmental duplication regions are often intractable. Using a read depth approach based on next-generation sequencing, we examined genome-wide copy number differences among five taurine (three Angus, one ...
Distributions on unbounded moment spaces and random moment sequences
Dette, Holger; Nagel, Jan
2012-01-01
In this paper we define distributions on moment spaces corresponding to measures on the real line with an unbounded support. We identify these distributions as limiting distributions of random moment vectors defined on compact moment spaces and as distributions corresponding to random spectral measures associated with the Jacobi, Laguerre and Hermite ensemble from random matrix theory. For random vectors on the unbounded moment spaces we prove a central limit theorem where the centering vecto...
Partial summations of stationary sequences of non-Gaussian random variables
DEFF Research Database (Denmark)
Mohr, Gunnar; Ditlevsen, Ove Dalager
1996-01-01
The distribution of the sum of a finite number of identically distributed random variables is in many cases easily determined given that the variables are independent. The moments of any order of the sum can always be expressed by the moments of the single term without computational problems...... of convergence of the distribution of a sum (or an integral) of mutually dependent random variables to the Gaussian distribution. The paper is closely related to the work in Ditlevsen el al. [Ditlevsen, O., Mohr, G. & Hoffmeyer, P. Integration of non-Gaussian fields. Prob. Engng Mech 11 (1996) 15-23](2)........ However, in the case of dependency between the terms even calculation of a few of the first moments of the sum presents serious computational problems. By use of computerized symbol manipulations it is practicable to obtain exact moments of partial sums of stationary sequences of mutually dependent...
Mathematical conversations multicolor problems, problems in the theory of numbers, and random walks
Dynkin, E B
2006-01-01
Comprises Multicolor Problems, dealing with map-coloring problems; Problems in the Theory of Numbers, an elementary introduction to algebraic number theory; Random Walks, addressing basic problems in probability theory. 1963 edition.
A Novel Method for Increasing the Entropy of a Sequence of Independent, Discrete Random Variables
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Mieczyslaw Jessa
2015-10-01
Full Text Available In this paper, we propose a novel method for increasing the entropy of a sequence of independent, discrete random variables with arbitrary distributions. The method uses an auxiliary table and a novel theorem that concerns the entropy of a sequence in which the elements are a bitwise exclusive-or sum of independent discrete random variables.
Sequenza: allele-specific copy number and mutation profiles from tumor sequencing data
DEFF Research Database (Denmark)
Favero, Francesco; Joshi, Tejal; Marquard, Andrea Marion
2015-01-01
specimen, by intratumor heterogeneity, and by the sheer size of the raw data. In particular, determination of copy number variations from exome sequencing data alone has proven difficult; thus SNP arrays have often been used for this task. Recently, algorithms to estimate absolute, but not allele...... data simulating normal-tumor admixtures, Sequenza detected the correct ploidy in samples with tumor content as low as 30%. Conclusions : The agreement between Sequenza and SNP array-based copy number profiles suggests that exome sequencing alone is sufficient not only for identifying small scale......Background : Exome or whole genome deep sequencing of tumor DNA along with paired normal DNA can potentially provide a detailed picture of the somatic mutations that characterize the tumor. However, analysis of such sequence data can be complicated by the presence of normal cells in the tumor...
Test-enhanced web-based learning: optimizing the number of questions (a randomized crossover trial).
Cook, David A; Thompson, Warren G; Thomas, Kris G
2014-01-01
Questions enhance learning in Web-based courses, but preliminary evidence suggests that too many questions may interfere with learning. The authors sought to determine how varying the number of self-assessment questions affects knowledge outcomes in a Web-based course. The authors conducted a randomized crossover trial in one internal medicine and one family medicine residency program between January 2009 and July 2010. Eight Web-based modules on ambulatory medicine topics were developed, with varying numbers of self-assessment questions (0, 1, 5, 10, or 15). Participants completed modules in four different formats each year, with sequence randomly assigned. Participants completed a pretest for half their modules. Outcomes included knowledge, completion time, and module ratings. One hundred eighty residents provided data. The mean (standard error) percent correct knowledge score was 53.2 (0.8) for pretests and 73.7 (0.5) for posttests. In repeated-measures analysis pooling all data, mean posttest knowledge scores were highest for the 10- and 15-question formats (75.7 [1.1] and 74.4 [1.0], respectively) and lower for 0-, 1-, and 5-question formats (73.1 [1.3], 72.9 [1.0], and 72.8 [1.5], respectively); P = .04 for differences across all modules. Modules with more questions generally took longer to complete and were rated higher, although differences were small. Residents most often identified 10 questions as ideal. Posttest knowledge scores were higher for modules that included a pretest (75.4 [0.9] versus 72.2 [0.9]; P = .0002). Increasing the number of self-assessment questions improves learning until a plateau beyond which additional questions do not add value.
High-speed true random number generation based on paired memristors for security electronics
Zhang, Teng; Yin, Minghui; Xu, Changmin; Lu, Xiayan; Sun, Xinhao; Yang, Yuchao; Huang, Ru
2017-11-01
True random number generator (TRNG) is a critical component in hardware security that is increasingly important in the era of mobile computing and internet of things. Here we demonstrate a TRNG using intrinsic variation of memristors as a natural source of entropy that is otherwise undesirable in most applications. The random bits were produced by cyclically switching a pair of tantalum oxide based memristors and comparing their resistance values in the off state, taking advantage of the more pronounced resistance variation compared with that in the on state. Using an alternating read scheme in the designed TRNG circuit, the unbiasedness of the random numbers was significantly improved, and the bitstream passed standard randomness tests. The Pt/TaO x /Ta memristors fabricated in this work have fast programming/erasing speeds of ∼30 ns, suggesting a high random number throughput. The approach proposed here thus holds great promise for physically-implemented random number generation.
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Dug Hun Hong
1999-01-01
Full Text Available Let {Xij} be a double sequence of pairwise independent random variables. If P{|Xmn|≥t}≤P{|X|≥t} for all nonnegative real numbers t and E|X|p(log+|X|3<∞, for 1
random variables under the conditions E|X|p(log+|X|r+1<∞,E|X|p(log+|X|r−1<∞, respectively, thus, extending Choi and Sung's result [1] of the one-dimensional case.
Directory of Open Access Journals (Sweden)
Varala Kranthi
2007-05-01
Full Text Available Abstract Background Extensive computational and database tools are available to mine genomic and genetic databases for model organisms, but little genomic data is available for many species of ecological or agricultural significance, especially those with large genomes. Genome surveys using conventional sequencing techniques are powerful, particularly for detecting sequences present in many copies per genome. However these methods are time-consuming and have potential drawbacks. High throughput 454 sequencing provides an alternative method by which much information can be gained quickly and cheaply from high-coverage surveys of genomic DNA. Results We sequenced 78 million base-pairs of randomly sheared soybean DNA which passed our quality criteria. Computational analysis of the survey sequences provided global information on the abundant repetitive sequences in soybean. The sequence was used to determine the copy number across regions of large genomic clones or contigs and discover higher-order structures within satellite repeats. We have created an annotated, online database of sequences present in multiple copies in the soybean genome. The low bias of pyrosequencing against repeat sequences is demonstrated by the overall composition of the survey data, which matches well with past estimates of repetitive DNA content obtained by DNA re-association kinetics (Cot analysis. Conclusion This approach provides a potential aid to conventional or shotgun genome assembly, by allowing rapid assessment of copy number in any clone or clone-end sequence. In addition, we show that partial sequencing can provide access to partial protein-coding sequences.
Doing Better by Getting Worse: Posthypnotic Amnesia Improves Random Number Generation
Terhune, Devin Blair; Brugger, Peter
2011-01-01
Although forgetting is often regarded as a deficit that we need to control to optimize cognitive functioning, it can have beneficial effects in a number of contexts. We examined whether disrupting memory for previous numerical responses would attenuate repetition avoidance (the tendency to avoid repeating the same number) during random number generation and thereby improve the randomness of responses. Low suggestible and low dissociative and high dissociative highly suggestible individuals completed a random number generation task in a control condition, following a posthypnotic amnesia suggestion to forget previous numerical responses, and in a second control condition following the cancellation of the suggestion. High dissociative highly suggestible participants displayed a selective increase in repetitions during posthypnotic amnesia, with equivalent repetition frequency to a random system, whereas the other two groups exhibited repetition avoidance across conditions. Our results demonstrate that temporarily disrupting memory for previous numerical responses improves random number generation. PMID:22195022
Doing better by getting worse: posthypnotic amnesia improves random number generation.
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Devin Blair Terhune
Full Text Available Although forgetting is often regarded as a deficit that we need to control to optimize cognitive functioning, it can have beneficial effects in a number of contexts. We examined whether disrupting memory for previous numerical responses would attenuate repetition avoidance (the tendency to avoid repeating the same number during random number generation and thereby improve the randomness of responses. Low suggestible and low dissociative and high dissociative highly suggestible individuals completed a random number generation task in a control condition, following a posthypnotic amnesia suggestion to forget previous numerical responses, and in a second control condition following the cancellation of the suggestion. High dissociative highly suggestible participants displayed a selective increase in repetitions during posthypnotic amnesia, with equivalent repetition frequency to a random system, whereas the other two groups exhibited repetition avoidance across conditions. Our results demonstrate that temporarily disrupting memory for previous numerical responses improves random number generation.
CNVkit: Genome-Wide Copy Number Detection and Visualization from Targeted DNA Sequencing.
Directory of Open Access Journals (Sweden)
Eric Talevich
2016-04-01
Full Text Available Germline copy number variants (CNVs and somatic copy number alterations (SCNAs are of significant importance in syndromic conditions and cancer. Massively parallel sequencing is increasingly used to infer copy number information from variations in the read depth in sequencing data. However, this approach has limitations in the case of targeted re-sequencing, which leaves gaps in coverage between the regions chosen for enrichment and introduces biases related to the efficiency of target capture and library preparation. We present a method for copy number detection, implemented in the software package CNVkit, that uses both the targeted reads and the nonspecifically captured off-target reads to infer copy number evenly across the genome. This combination achieves both exon-level resolution in targeted regions and sufficient resolution in the larger intronic and intergenic regions to identify copy number changes. In particular, we successfully inferred copy number at equivalent to 100-kilobase resolution genome-wide from a platform targeting as few as 293 genes. After normalizing read counts to a pooled reference, we evaluated and corrected for three sources of bias that explain most of the extraneous variability in the sequencing read depth: GC content, target footprint size and spacing, and repetitive sequences. We compared the performance of CNVkit to copy number changes identified by array comparative genomic hybridization. We packaged the components of CNVkit so that it is straightforward to use and provides visualizations, detailed reporting of significant features, and export options for integration into existing analysis pipelines. CNVkit is freely available from https://github.com/etal/cnvkit.
Non-periodic pseudo-random numbers used in Monte Carlo calculations
Barberis, Gaston E.
2007-09-01
The generation of pseudo-random numbers is one of the interesting problems in Monte Carlo simulations, mostly because the common computer generators produce periodic numbers. We used simple pseudo-random numbers generated with the simplest chaotic system, the logistic map, with excellent results. The numbers generated in this way are non-periodic, which we demonstrated for 1013 numbers, and they are obtained in a deterministic way, which allows to repeat systematically any calculation. The Monte Carlo calculations are the ideal field to apply these numbers, and we did it for simple and more elaborated cases. Chemistry and Information Technology use this kind of simulations, and the application of this numbers to quantum Monte Carlo and cryptography is immediate. I present here the techniques to calculate, analyze and use these pseudo-random numbers, show that they lack periodicity up to 1013 numbers and that they are not correlated.
Mapping the acquisition of the number word sequence in the first year of school
Gould, Peter
2017-03-01
Learning to count and to produce the correct sequence of number words in English is not a simple process. In NSW government schools taking part in Early Action for Success, over 800 students in each of the first 3 years of school were assessed every 5 weeks over the school year to determine the highest correct oral count they could produce. Rather than displaying a steady increase in the accurate sequence of the number words produced, the kindergarten data reported here identified clear, substantial hurdles in the acquisition of the counting sequence. The large-scale, longitudinal data also provided evidence of learning to count through the teens being facilitated by the semi-regular structure of the number words in English. Instead of occurring as hurdles to starting the next counting sequence, number words corresponding to some multiples of ten (10, 20 and 100) acted as if they were rest points. These rest points appear to be artefacts of how the counting sequence is acquired.
Interference Suppression Performance of Automotive UWB Radars Using Pseudo Random Sequences
Directory of Open Access Journals (Sweden)
I. Pasya
2015-12-01
Full Text Available Ultra wideband (UWB automotive radars have attracted attention from the viewpoint of reducing traffic accidents. The performance of automotive radars may be degraded by interference from nearby radars using the same frequency. In this study, a scenario where two cars pass each other on a road was considered. Considering the utilization of cross-polarization, the desired-to-undesired signal power ratio (DUR was found to vary approximately from -10 to 30 dB. Different pseudo random sequences were employed for spectrum spreading the different radar signals to mitigate the interference effects. This paper evaluates the interference suppression provided by maximum length sequence (MLS and Gold sequence (GS through numerical simulations of the radar’s performance in terms of probability of false alarm and probability of detection. It was found that MLS and GS yielded nearly the same performance when the DUR is -10 dB (worst case; for example when fixing the probability of false alarm to 0.0001, the probabilities of detection were 0.964 and 0.946 respectively. The GS are more advantageous than MLS due to larger number of different sequences having the same length in GS than in MLS.
Energy Technology Data Exchange (ETDEWEB)
Ethridge, C.D.; Worth, G.M.
1977-01-01
A scientific calculating system for large distributed-task processing systems and for small isolated intelligent data acquisition and instrumentation systems is established with a number-oriented microprocessor sequenced by a single-component microcomputer. A MOS/LSI number-oriented microprocessor provides the scientific calculating capability with Reverse Polish Notation data entry. Input data sequencing, computation processing, intermediate result comparison, answer display and/or answer feed-back to master processors is controlled by a single-component microcomputer. 3 figures, 1 table.
Natural vs. random protein sequences: Discovering combinatorics properties on amino acid words.
Santoni, Daniele; Felici, Giovanni; Vergni, Davide
2016-02-21
Casual mutations and natural selection have driven the evolution of protein amino acid sequences that we observe at present in nature. The question about which is the dominant force of proteins evolution is still lacking of an unambiguous answer. Casual mutations tend to randomize protein sequences while, in order to have the correct functionality, one expects that selection mechanisms impose rigid constraints on amino acid sequences. Moreover, one also has to consider that the space of all possible amino acid sequences is so astonishingly large that it could be reasonable to have a well tuned amino acid sequence indistinguishable from a random one. In order to study the possibility to discriminate between random and natural amino acid sequences, we introduce different measures of association between pairs of amino acids in a sequence, and apply them to a dataset of 1047 natural protein sequences and 10,470 random sequences, carefully generated in order to preserve the relative length and amino acid distribution of the natural proteins. We analyze the multidimensional measures with machine learning techniques and show that, to a reasonable extent, natural protein sequences can be differentiated from random ones. Copyright © 2015 Elsevier Ltd. All rights reserved.
High-speed quantum-random number generation by continuous measurement of arrival time of photons.
Yan, Qiurong; Zhao, Baosheng; Hua, Zhang; Liao, Qinghong; Yang, Hao
2015-07-01
We demonstrate a novel high speed and multi-bit optical quantum random number generator by continuously measuring arrival time of photons with a common starting point. To obtain the unbiased and post-processing free random bits, the measured photon arrival time is converted into the sum of integral multiple of a fixed period and a phase time. Theoretical and experimental results show that the phase time is an independent and uniform random variable. A random bit extraction method by encoding the phase time is proposed. An experimental setup has been built and the unbiased random bit generation rate could reach 128 Mb/s, with random bit generation efficiency of 8 bits per detected photon. The random numbers passed all tests in the statistical test suite.
Directory of Open Access Journals (Sweden)
Paul eMiller
2013-05-01
Full Text Available Randomly connected recurrent networks of excitatory groups of neurons can possess a multitude of attractor states. When the internal excitatory synapses of these networks are depressing, the attractor states can be destabilized with increasing input. This leads to an itinerancy, where with either repeated transient stimuli, or increasing duration of a single stimulus, the network activity advances through sequences of attractor states. We find that the resulting network state, which persists beyond stimulus offset, can encode the number of stimuli presented via a distributed representation of neural activity with non-monotonic tuning curves for most neurons. Increased duration of a single stimulus is encoded via different distributed representations, so unlike an integrator, the network distinguishes separate successive presentations of a short stimulus from a single presentation of a longer stimulus with equal total duration. Moreover, different amplitudes of stimulus cause new, distinct activity patterns, such that changes in stimulus number, duration and amplitude can be distinguished from each other. These properties of the network depend on dynamic depressing synapses, as they disappear if synapses are static. Thus short-term synaptic depression allows a network to store separately the different dynamic properties of a spatially constant stimulus.
ReadDepth: a parallel R package for detecting copy number alterations from short sequencing reads.
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Christopher A Miller
2011-01-01
Full Text Available Copy number alterations are important contributors to many genetic diseases, including cancer. We present the readDepth package for R, which can detect these aberrations by measuring the depth of coverage obtained by massively parallel sequencing of the genome. In addition to achieving higher accuracy than existing packages, our tool runs much faster by utilizing multi-core architectures to parallelize the processing of these large data sets. In contrast to other published methods, readDepth does not require the sequencing of a reference sample, and uses a robust statistical model that accounts for overdispersed data. It includes a method for effectively increasing the resolution obtained from low-coverage experiments by utilizing breakpoint information from paired end sequencing to do positional refinement. We also demonstrate a method for inferring copy number using reads generated by whole-genome bisulfite sequencing, thus enabling integrative study of epigenomic and copy number alterations. Finally, we apply this tool to two genomes, showing that it performs well on genomes sequenced to both low and high coverage. The readDepth package runs on Linux and MacOSX, is released under the Apache 2.0 license, and is available at http://code.google.com/p/readdepth/.
Some Additions to the Fuzzy Convergent and Fuzzy Bounded Sequence Spaces of Fuzzy Numbers
M. Şengönül; Zararsız, Z.
2011-01-01
Some properties of the fuzzy convergence and fuzzy boundedness of a sequence of fuzzy numbers were studied in Choi (1996). In this paper, we have consider, some important problems on these spaces and shown that these spaces are fuzzy complete module spaces. Also, the fuzzy α-, fuzzy β-, and fuzzy γ-duals of the fuzzy module spaces of fuzzy numbers have been computeded, and some matrix transformations are given.
Efficient Raman generation in a waveguide: A route to ultrafast quantum random number generation
Energy Technology Data Exchange (ETDEWEB)
England, D. G.; Bustard, P. J.; Moffatt, D. J.; Nunn, J.; Lausten, R.; Sussman, B. J., E-mail: ben.sussman@nrc.ca [National Research Council of Canada, 100 Sussex Drive, Ottawa, Ontario K1A 0R6 (Canada)
2014-02-03
The inherent uncertainty in quantum mechanics offers a source of true randomness which can be used to produce unbreakable cryptographic keys. We discuss the development of a high-speed random number generator based on the quantum phase fluctuations in spontaneously initiated stimulated Raman scattering (SISRS). We utilize the tight confinement and long interaction length available in a Potassium Titanyl Phosphate waveguide to generate highly efficient SISRS using nanojoule pulse energies, reducing the high pump power requirements of the previous approaches. We measure the random phase of the Stokes output using a simple interferometric setup to yield quantum random numbers at 145 Mbps.
Detection of clinically relevant copy number variants with whole-exome sequencing
Ligt, J. de; Boone, P.M.; Pfundt, R.; Vissers, L.E.L.M.; Richmond, T.; Geoghegan, J.; O'Moore, K.; Leeuw, N. de; Shaw, C.; Brunner, H.G.; Lupski, J.R.; Veltman, J.A.; Hehir-Kwa, J.Y.
2013-01-01
Copy number variation (CNV) is a common source of genetic variation that has been implicated in many genomic disorders. This has resulted in the widespread application of genomic microarrays as a first-tier diagnostic tool for CNV detection. More recently, whole-exome sequencing (WES) has been
MSRV pol sequence copy number as a potential marker of multiple sclerosis.
Zawada, Mariola; Liwień, Izabela; Pernak, Monika; Januszkiewicz-Lewandowska, Danuta; Nowicka-Kujawska, Karina; Rembowska, Jolanta; Lewandowski, Krzysztof; Hertmanowska, Hanna; Wender, Mieczysław; Nowak, Jerzy
2003-01-01
Multiple sclerosis (MS) is a neurological disease in which demyelination in the brain and spinal cord is observed. The causal influence of bacterial/viral infections and genetic/immune factors in the etiology of multiple sclerosis is suggested. Multiple sclerosis-related retrovirus (MSRV) is one of the potential agents, which can lead to development of the disease. The aim of cytogenetic studies was assessment of MSRV pol sequence copy number in patients with MS compared to normal individuals. Cytogenetic slides with interphase nuclei and extended chromatin fibers were prepared from peripheral blood of 16 patients with MS and 10 healthy individuals. Fluorescence in situ hybridization (FISH) with biotinylated product of polymerase chain reaction was used in order to analyze MSRV pol sequence copy number in the examined material. Detection of MSRV pol probe was carried out by immunological reaction with avidin-fluorescein and biotinylated anti-avidin. MSRV pol sequence copy number was significantly greater in MS patients than in normal individuals. Using FISH technique to extended chromatin fibers, it was observed that MSRV pol exists as tandem repeats on various chromosomes. The increased number of MSRV pol sequence has been found on chromatin fibers of MS patients as compared to healthy controls.
Long insert whole genome sequencing for copy number variant and translocation detection.
Liang, Winnie S; Aldrich, Jessica; Tembe, Waibhav; Kurdoglu, Ahmet; Cherni, Irene; Phillips, Lori; Reiman, Rebecca; Baker, Angela; Weiss, Glen J; Carpten, John D; Craig, David W
2014-01-01
As next-generation sequencing continues to have an expanding presence in the clinic, the identification of the most cost-effective and robust strategy for identifying copy number changes and translocations in tumor genomes is needed. We hypothesized that performing shallow whole genome sequencing (WGS) of 900-1000-bp inserts (long insert WGS, LI-WGS) improves our ability to detect these events, compared with shallow WGS of 300-400-bp inserts. A priori analyses show that LI-WGS requires less sequencing compared with short insert WGS to achieve a target physical coverage, and that LI-WGS requires less sequence coverage to detect a heterozygous event with a power of 0.99. We thus developed an LI-WGS library preparation protocol based off of Illumina's WGS library preparation protocol and illustrate the feasibility of performing LI-WGS. We additionally applied LI-WGS to three separate tumor/normal DNA pairs collected from patients diagnosed with different cancers to demonstrate our application of LI-WGS on actual patient samples for identification of somatic copy number alterations and translocations. With the evolution of sequencing technologies and bioinformatics analyses, we show that modifications to current approaches may improve our ability to interrogate cancer genomes.
The sequence to hydrogenate coronene cations: A journey guided by magic numbers
Cazaux, Stéphanie; Rougeau, Nathalie; Reitsma, Geert; Hoekstra, Ronnie; Teillet-Billy, Dominique; Morisset, Sabine; Spaans, Marco; Schlathölter, Thomas
2016-01-01
The understanding of hydrogen attachment to carbonaceous surfaces is essential to a wide variety of research fields and technologies such as hydrogen storage for transportation, precise localization of hydrogen in electronic devices and the formation of cosmic H2. For coronene cations as prototypical Polycyclic Aromatic Hydrocarbon (PAH) molecules, the existence of magic numbers upon hydrogenation was uncovered experimentally. Quantum chemistry calculations show that hydrogenation follows a site-specific sequence leading to the appearance of cations having 5, 11, or 17 hydrogen atoms attached, exactly the magic numbers found in the experiments. For these closed-shell cations, further hydrogenation requires appreciable structural changes associated with a high transition barrier. Controlling specific hydrogenation pathways would provide the possibility to tune the location of hydrogen attachment and the stability of the system. The sequence to hydrogenate PAHs, leading to PAHs with magic numbers of H atoms att...
Random amplified polymorphic DNA (RAPD) and simple sequence ...
African Journals Online (AJOL)
To compare these two methods, genetic parameters were computed such as the number of polymorphic bands, average number of alleles per locus, effective number of alleles per locus, expected heterozygosity, effectiveness index of analysis and polymorphism information content (PIC). Better results were provided by ...
Long insert whole genome sequencing for copy number variant and translocation detection
Liang, Winnie S.; Aldrich, Jessica; Tembe, Waibhav; Kurdoglu, Ahmet; Cherni, Irene; Phillips, Lori; Reiman, Rebecca; Baker, Angela; Weiss, Glen J.; Carpten, John D.; Craig, David W.
2013-01-01
As next-generation sequencing continues to have an expanding presence in the clinic, the identification of the most cost-effective and robust strategy for identifying copy number changes and translocations in tumor genomes is needed. We hypothesized that performing shallow whole genome sequencing (WGS) of 900–1000-bp inserts (long insert WGS, LI-WGS) improves our ability to detect these events, compared with shallow WGS of 300–400-bp inserts. A priori analyses show that LI-WGS requires less s...
Raw and Central Moments of Binomial Random Variables via Stirling Numbers
Griffiths, Martin
2013-01-01
We consider here the problem of calculating the moments of binomial random variables. It is shown how formulae for both the raw and the central moments of such random variables may be obtained in a recursive manner utilizing Stirling numbers of the first kind. Suggestions are also provided as to how students might be encouraged to explore this…
Strong Laws of Large Numbers for Arrays of Rowwise NA and LNQD Random Variables
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Jiangfeng Wang
2011-01-01
Full Text Available Some strong laws of large numbers and strong convergence properties for arrays of rowwise negatively associated and linearly negative quadrant dependent random variables are obtained. The results obtained not only generalize the result of Hu and Taylor to negatively associated and linearly negative quadrant dependent random variables, but also improve it.
Note: A 10 Gbps real-time post-processing free physical random number generator chip
Qian, Yi; Liang, Futian; Wang, Xinzhe; Li, Feng; Chen, Lian; Jin, Ge
2017-09-01
A random number generator with high data rate, small size, and low power consumption is essential for a certain quantum key distribution (QKD) system. We designed a 10 Gbps random number generator ASIC, TRNG2016, for the QKD system. With a 6 mm × 6 mm QFN48 package, TRNG2016 has 10 independent physical random number generation channels, and each channel can work at a fixed frequency up to 1 Gbps. The random number generated by TRNG2016 can pass the NIST statistical tests without any post-processing. With 3.3 V IO power supply and 1.2 V core power supply, the typical power consumption of TRNG2016 is 773 mW with 10 channels on and running at 1 Gbps data rate.
Quantifying biodiversity and asymptotics for a sequence of random strings.
Koyano, Hitoshi; Kishino, Hirohisa
2010-06-01
We present a methodology for quantifying biodiversity at the sequence level by developing the probability theory on a set of strings. Further, we apply our methodology to the problem of quantifying the population diversity of microorganisms in several extreme environments and digestive organs and reveal the relation between microbial diversity and various environmental parameters.
Recommendations and illustrations for the evaluation of photonic random number generators
Hart, Joseph D.; Terashima, Yuta; Uchida, Atsushi; Baumgartner, Gerald B.; Murphy, Thomas E.; Roy, Rajarshi
2017-09-01
The never-ending quest to improve the security of digital information combined with recent improvements in hardware technology has caused the field of random number generation to undergo a fundamental shift from relying solely on pseudo-random algorithms to employing optical entropy sources. Despite these significant advances on the hardware side, commonly used statistical measures and evaluation practices remain ill-suited to understand or quantify the optical entropy that underlies physical random number generation. We review the state of the art in the evaluation of optical random number generation and recommend a new paradigm: quantifying entropy generation and understanding the physical limits of the optical sources of randomness. In order to do this, we advocate for the separation of the physical entropy source from deterministic post-processing in the evaluation of random number generators and for the explicit consideration of the impact of the measurement and digitization process on the rate of entropy production. We present the Cohen-Procaccia estimate of the entropy rate h (𝜖 ,τ ) as one way to do this. In order to provide an illustration of our recommendations, we apply the Cohen-Procaccia estimate as well as the entropy estimates from the new NIST draft standards for physical random number generators to evaluate and compare three common optical entropy sources: single photon time-of-arrival detection, chaotic lasers, and amplified spontaneous emission.
Random Coding Bounds for DNA Codes Based on Fibonacci Ensembles of DNA Sequences
2008-07-01
Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, Paperwork Reduction Project (0704-0188) Washington, DC...COVERED (From - To) 6 Jul 08 – 11 Jul 08 4. TITLE AND SUBTITLE RANDOM CODING BOUNDS FOR DNA CODES BASED ON FIBONACCI ENSEMBLES OF DNA SEQUENCES...sequences which are generalizations of the Fibonacci sequences. 15. SUBJECT TERMS DNA Codes, Fibonacci Ensembles, DNA Computing, Code Optimization 16
Directory of Open Access Journals (Sweden)
Jack A Gilbert
2008-08-01
Full Text Available Sequencing the expressed genetic information of an ecosystem (metatranscriptome can provide information about the response of organisms to varying environmental conditions. Until recently, metatranscriptomics has been limited to microarray technology and random cloning methodologies. The application of high-throughput sequencing technology is now enabling access to both known and previously unknown transcripts in natural communities.We present a study of a complex marine metatranscriptome obtained from random whole-community mRNA using the GS-FLX Pyrosequencing technology. Eight samples, four DNA and four mRNA, were processed from two time points in a controlled coastal ocean mesocosm study (Bergen, Norway involving an induced phytoplankton bloom producing a total of 323,161,989 base pairs. Our study confirms the finding of the first published metatranscriptomic studies of marine and soil environments that metatranscriptomics targets highly expressed sequences which are frequently novel. Our alternative methodology increases the range of experimental options available for conducting such studies and is characterized by an exceptional enrichment of mRNA (99.92% versus ribosomal RNA. Analysis of corresponding metagenomes confirms much higher levels of assembly in the metatranscriptomic samples and a far higher yield of large gene families with >100 members, approximately 91% of which were novel.This study provides further evidence that metatranscriptomic studies of natural microbial communities are not only feasible, but when paired with metagenomic data sets, offer an unprecedented opportunity to explore both structure and function of microbial communities--if we can overcome the challenges of elucidating the functions of so many never-seen-before gene families.
Strenge, Hans; Lesmana, Cokorda Bagus Jaya; Suryani, Luh Ketut
2009-08-01
Verbal random number generation is a procedurally simple task to assess executive function and appears ideally suited for the use under diverse settings in cross-cultural research. The objective of this study was to examine ethnic group differences between young adults in Bali (Indonesia) and Kiel (Germany): 50 bilingual healthy students, 30 Balinese and 20 Germans, attempted to generate a random sequence of the digits 1 to 9. In Balinese participants, randomization was done in Balinese (native language L1) and Indonesian (first foreign language L2), in German subjects in the German (L1) and English (L2) languages. 10 of 30 Balinese (33%), but no Germans, were unable to inhibit habitual counting in more than half of the responses. The Balinese produced significantly more nonrandom responses than the Germans with higher rates of counting and significantly less occurrence of the digits 2 and 3 in L1 compared with L2. Repetition and cycling behavior did not differ between the four languages. The findings highlight the importance of taking into account culture-bound psychosocial factors for Balinese individuals when administering and interpreting a random number generation test.
Random amplified polymorphic DNA (RAPD) and simple sequence ...
African Journals Online (AJOL)
Administrator
2011-06-06
Jun 6, 2011 ... of polymorphic bands, average number of alleles per locus, effective .... Materials for DNA isolation were obtained from a set of 5 to 7 plants ..... Among factors that might have contributed to ... Inheritance of RAPDs in F1 hybrids of corn. ... by using cluster analysis of RAPD molecular marker, phenotype and.
The intersection numbers of the p-spin curves from random matrix theory
Brézin, E.; Hikami, S.
2013-02-01
The intersection numbers of p-spin curves are computed through correlation functions of Gaussian ensembles of random matrices in an external matrix source. The p-dependence of intersection numbers is determined as polynomial in p; the large p behavior is also considered. The analytic continuation of intersection numbers to negative values of p is discussed in relation to SL(2,R)/U(1) black hole sigma model.
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Nicholas J. Sexton
2014-07-01
Full Text Available Random number generation (RNG is a complex cognitive task for human subjects, requiring deliberative control to avoid production of habitual, stereotyped sequences. Under various manipulations (e.g., speeded responding, transcranial magnetic stimulation, or neurological damage the performance of human subjects deteriorates, as reflected in a number of qualitatively distinct, dissociable biases. For example, the intrusion of stereotyped behaviour (e.g., counting increases at faster rates of generation. Theoretical accounts of the task postulate that it requires the integrated operation of multiple, computationally heterogeneous cognitive control ('executive' processes. We present a computational model of RNG, within the framework of a novel, neuropsychologically-inspired cognitive architecture, ESPro. Manipulating the rate of sequence generation in the model reproduced a number of key effects observed in empirical studies, including increasing sequence stereotypy at faster rates. Within the model, this was due to time limitations on the interaction of supervisory control processes, namely, task setting, proposal of responses, monitoring, and response inhibition. The model thus supports the fractionation of executive function into multiple, computationally heterogeneous processes.
RefCNV: Identification of Gene-Based Copy Number Variants Using Whole Exome Sequencing.
Chang, Lun-Ching; Das, Biswajit; Lih, Chih-Jian; Si, Han; Camalier, Corinne E; McGregor, Paul M; Polley, Eric
2016-01-01
With rapid advances in DNA sequencing technologies, whole exome sequencing (WES) has become a popular approach for detecting somatic mutations in oncology studies. The initial intent of WES was to characterize single nucleotide variants, but it was observed that the number of sequencing reads that mapped to a genomic region correlated with the DNA copy number variants (CNVs). We propose a method RefCNV that uses a reference set to estimate the distribution of the coverage for each exon. The construction of the reference set includes an evaluation of the sources of variability in the coverage distribution. We observed that the processing steps had an impact on the coverage distribution. For each exon, we compared the observed coverage with the expected normal coverage. Thresholds for determining CNVs were selected to control the false-positive error rate. RefCNV prediction correlated significantly (r = 0.96-0.86) with CNV measured by digital polymerase chain reaction for MET (7q31), EGFR (7p12), or ERBB2 (17q12) in 13 tumor cell lines. The genome-wide CNV analysis showed a good overall correlation (Spearman's coefficient = 0.82) between RefCNV estimation and publicly available CNV data in Cancer Cell Line Encyclopedia. RefCNV also showed better performance than three other CNV estimation methods in genome-wide CNV analysis.
An empirical study of the complexity and randomness of prediction error sequences
Ratsaby, Joel
2011-07-01
We investigate a population of binary mistake sequences that result from learning with parametric models of different order. We obtain estimates of their error, algorithmic complexity and divergence from a purely random Bernoulli sequence. We study the relationship of these variables to the learner's information density parameter which is defined as the ratio between the lengths of the compressed to uncompressed files that contain the learner's decision rule. The results indicate that good learners have a low information density ρ while bad learners have a high ρ. Bad learners generate mistake sequences that are atypically complex or diverge stochastically from a purely random Bernoulli sequence. Good learners generate typically complex sequences with low divergence from Bernoulli sequences and they include mistake sequences generated by the Bayes optimal predictor. Based on the static algorithmic interference model of [18] the learner here acts as a static structure which "scatters" the bits of an input sequence (to be predicted) in proportion to its information density ρ thereby deforming its randomness characteristics.
Quantum random number generation enhanced by weak-coherent states interference.
Ferreira da Silva, T; Xavier, G B; Amaral, G C; Temporão, G P; von der Weid, J P
2016-08-22
We propose and demonstrate a technique for quantum random number generation based on the random population of the output spatial modes of a beam splitter when both inputs are simultaneously fed with indistinguishable weak coherent states. We simulate and experimentally validate the probability of generation of random bits as a function of the average photon number per input, and compare it to the traditional approach of a single weak coherent state transmitted through a beam-splitter, showing an improvement of up to 32%. The ensuing interference phenomenon reduces the probability of coincident counts between the detectors associated with bits 0 and 1, thus increasing the probability of occurrence of a valid output. A long bit string is assessed by a standard randomness test suite with good confidence. Our proposal can be easily implemented and opens attractive performance gains without a significant trade-off.
Note: Fully integrated 3.2 Gbps quantum random number generator with real-time extraction
Energy Technology Data Exchange (ETDEWEB)
Zhang, Xiao-Guang; Nie, You-Qi; Liang, Hao; Zhang, Jun, E-mail: zhangjun@ustc.edu.cn; Pan, Jian-Wei [Hefei National Laboratory for Physical Sciences at the Microscale and Department of Modern Physics, University of Science and Technology of China, Hefei, Anhui 230026 (China); CAS Center for Excellence and Synergetic Innovation Center in Quantum Information and Quantum Physics, University of Science and Technology of China, Hefei, Anhui 230026 (China); Zhou, Hongyi; Ma, Xiongfeng [Center for Quantum Information, Institute for Interdisciplinary Information Sciences, Tsinghua University, Beijing 100084 (China)
2016-07-15
We present a real-time and fully integrated quantum random number generator (QRNG) by measuring laser phase fluctuations. The QRNG scheme based on laser phase fluctuations is featured for its capability of generating ultra-high-speed random numbers. However, the speed bottleneck of a practical QRNG lies on the limited speed of randomness extraction. To close the gap between the fast randomness generation and the slow post-processing, we propose a pipeline extraction algorithm based on Toeplitz matrix hashing and implement it in a high-speed field-programmable gate array. Further, all the QRNG components are integrated into a module, including a compact and actively stabilized interferometer, high-speed data acquisition, and real-time data post-processing and transmission. The final generation rate of the QRNG module with real-time extraction can reach 3.2 Gbps.
Effective normalization for copy number variation detection from whole genome sequencing.
Janevski, Angel; Varadan, Vinay; Kamalakaran, Sitharthan; Banerjee, Nilanjana; Dimitrova, Nevenka
2012-01-01
Whole genome sequencing enables a high resolution view of the human genome and provides unique insights into genome structure at an unprecedented scale. There have been a number of tools to infer copy number variation in the genome. These tools, while validated, also include a number of parameters that are configurable to genome data being analyzed. These algorithms allow for normalization to account for individual and population-specific effects on individual genome CNV estimates but the impact of these changes on the estimated CNVs is not well characterized. We evaluate in detail the effect of normalization methodologies in two CNV algorithms FREEC and CNV-seq using whole genome sequencing data from 8 individuals spanning four populations. We apply FREEC and CNV-seq to a sequencing data set consisting of 8 genomes. We use multiple configurations corresponding to different read-count normalization methodologies in FREEC, and statistically characterize the concordance of the CNV calls between FREEC configurations and the analogous output from CNV-seq. The normalization methodologies evaluated in FREEC are: GC content, mappability and control genome. We further stratify the concordance analysis within genic, non-genic, and a collection of validated variant regions. The GC content normalization methodology generates the highest number of altered copy number regions. Both mappability and control genome normalization reduce the total number and length of copy number regions. Mappability normalization yields Jaccard indices in the 0.07 - 0.3 range, whereas using a control genome normalization yields Jaccard index values around 0.4 with normalization based on GC content. The most critical impact of using mappability as a normalization factor is substantial reduction of deletion CNV calls. The output of another method based on control genome normalization, CNV-seq, resulted in comparable CNV call profiles, and substantial agreement in variable gene and CNV region calls
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Zhen ePeng
2014-03-01
Full Text Available Complexity is a hallmark of intelligent behavior consisting both of regular patterns and random variation. To quantitatively assess the complexity and randomness of human motion, we designed a motor task in which we translated subjects' motion trajectories into strings of symbol sequences. In the first part of the experiment participants were asked to perform self-paced movements to create repetitive patterns, copy pre-specified letter sequences, and generate random movements. To investigate whether the degree of randomness can be manipulated, in the second part of the experiment participants were asked to perform unpredictable movements in the context of a pursuit game, where they received feedback from an online Bayesian predictor guessing their next move. We analyzed symbol sequences representing subjects' motion trajectories with five common complexity measures: predictability, compressibility, approximate entropy, Lempel-Ziv complexity, as well as effective measure complexity. We found that subjects’ self-created patterns were the most complex, followed by drawing movements of letters and self-paced random motion. We also found that participants could change the randomness of their behavior depending on context and feedback. Our results suggest that humans can adjust both complexity and regularity in different movement types and contexts and that this can be assessed with information-theoretic measures of the symbolic sequences generated from movement trajectories.
Haeseler, Friedrich
2003-01-01
Automatic sequences are sequences which are produced by a finite automaton. Although they are not random they may look as being random. They are complicated, in the sense of not being not ultimately periodic, they may look rather complicated, in the sense that it may not be easy to name the rule by which the sequence is generated, however there exists a rule which generates the sequence. The concept automatic sequences has special applications in algebra, number theory, finite automata and formal languages, combinatorics on words. The text deals with different aspects of automatic sequences, in particular:· a general introduction to automatic sequences· the basic (combinatorial) properties of automatic sequences· the algebraic approach to automatic sequences· geometric objects related to automatic sequences.
Tests of Sunspot Number Sequences: 2. Using Geomagnetic and Auroral Data
Lockwood, M.; Owens, M. J.; Barnard, L.; Scott, C. J.; Usoskin, I. G.; Nevanlinna, H.
2016-11-01
We compare four sunspot-number data sequences against geomagnetic and terrestrial auroral observations. The comparisons are made for the original Solar Influences Data Center (SIDC) composite of Wolf/Zürich/International sunspot number [R_{{ISNv}1}], the group sunspot number [RG] by Hoyt and Schatten ( Solar Phys. 181, 491, 1998), the new "backbone" group sunspot number [R_{BB}] by Svalgaard and Schatten ( Solar Phys., DOI: 10.1007/s11207-015-0815-8, 2016), and the "corrected" sunspot number [RC] by Lockwood, Owens, and Barnard ( J. Geophys. Res. 119, 5172, 2014a). Each sunspot number is fitted with terrestrial observations, or parameters derived from terrestrial observations to be linearly proportional to sunspot number, over a 30-year calibration interval of 1982 - 2012. The fits are then used to compute test sequences, which extend further back in time and which are compared to R_{{ISNv}1}, RG, R_{{BB}}, and RC. To study the long-term trends, comparisons are made using averages over whole solar cycles (minimum-to-minimum). The test variations are generated in four ways: i) using the IDV(1d) and IDV geomagnetic indices (for 1845 - 2013) fitted over the calibration interval using the various sunspot numbers and the phase of the solar cycle; ii) from the open solar flux (OSF) generated for 1845 - 2013 from four pairings of geomagnetic indices by Lockwood et al. ( Ann. Geophys. 32, 383, 2014a) and analysed using the OSF continuity model of Solanki, Schüssler, and Fligge ( Nature, 408, 445, 2000), which employs a constant fractional OSF loss rate; iii) the same OSF data analysed using the OSF continuity model of Owens and Lockwood ( J. Geophys. Res. 117, A04102, 2012), in which the fractional loss rate varies with the tilt of the heliospheric current sheet and hence with the phase of the solar cycle; iv) the occurrence frequency of low-latitude aurora for 1780 - 1980 from the survey of Legrand and Simon ( Ann. Geophys. 5, 161, 1987). For all cases, R_{BB} exceeds
Nguyen, Anh To; Tran, Thanh Tan; Hoang, Van Minh Tu; Nghiem, Ngoc My; Le, Nhu Nguyen Truc; Le, Thanh Thi My; Phan, Qui Tu; Truong, Khanh Huu; Le, Nhan Nguyen Thanh; Ho, Viet Lu; Do, Viet Chau; Ha, Tuan Manh; Nguyen, Hung Thanh; Nguyen, Chau Van Vinh; Thwaites, Guy; van Doorn, H Rogier; Le, Tan Van
2016-07-07
Hand, foot and mouth disease (HFMD) has become a major public health problem across the Asia-Pacific region, and is commonly caused by enterovirus A71 (EV-A71) and coxsackievirus A6 (CV-A6), CV-A10 and CV-A16. Generating pathogen whole-genome sequences is essential for understanding their evolutionary biology. The frequent replacements among EV serotypes and a limited numbers of available whole-genome sequences hinder the development of overlapping PCRs for whole-genome sequencing. We developed and evaluated a non-ribosomal random PCR (rPCR) and next-generation sequencing based assay for sequence-independent whole-genome amplification and sequencing of HFMD pathogens. A total of 16 EV-A71/CV-A6/CV-A10/CV-A16 PCR positive rectal/throat swabs (Cp values: 20.9-33.3) were used for assay evaluation. Our assay evidently outperformed the conventional rPCR in terms of the total number of EV-A71 reads and the percentage of EV-A71 reads: 2.6 % (1275/50,000 reads) vs. 0.1 % (31/50,000) and 6 % (3008/50,000) vs. 0.9 % (433/50,000) for two samples with Cp values of 30 and 26, respectively. Additionally the assay could generate genome sequences with the percentages of coverage of 94-100 % of 4 different enterovirus serotypes in 73 % of the tested samples, representing the first whole-genome sequences of CV-A6/10/16 from Vietnam, and could assign correctly serotyping results in 100 % of 24 tested specimens. In all but three the obtained consensuses of two replicates from the same sample were 100 % identical, suggesting that our assay is highly reproducible. In conclusion, we have successfully developed a non-ribosomal rPCR and next-generation sequencing based assay for sensitive detection and direct whole-genome sequencing of HFMD pathogens from clinical samples.
Human Y chromosome copy number variation in the next generation sequencing era and beyond.
Massaia, Andrea; Xue, Yali
2017-05-01
The human Y chromosome provides a fertile ground for structural rearrangements owing to its haploidy and high content of repeated sequences. The methodologies used for copy number variation (CNV) studies have developed over the years. Low-throughput techniques based on direct observation of rearrangements were developed early on, and are still used, often to complement array-based or sequencing approaches which have limited power in regions with high repeat content and specifically in the presence of long, identical repeats, such as those found in human sex chromosomes. Some specific rearrangements have been investigated for decades; because of their effects on fertility, or their outstanding evolutionary features, the interest in these has not diminished. However, following the flourishing of large-scale genomics, several studies have investigated CNVs across the whole chromosome. These studies sometimes employ data generated within large genomic projects such as the DDD study or the 1000 Genomes Project, and often survey large samples of healthy individuals without any prior selection. Novel technologies based on sequencing long molecules and combinations of technologies, promise to stimulate the study of Y-CNVs in the immediate future.
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Edward Nuhfer
2016-01-01
Full Text Available Self-assessment measures of competency are blends of an authentic self-assessment signal that researchers seek to measure and random disorder or "noise" that accompanies that signal. In this study, we use random number simulations to explore how random noise affects critical aspects of self-assessment investigations: reliability, correlation, critical sample size, and the graphical representations of self-assessment data. We show that graphical conventions common in the self-assessment literature introduce artifacts that invite misinterpretation. Troublesome conventions include: (y minus x vs. (x scatterplots; (y minus x vs. (x column graphs aggregated as quantiles; line charts that display data aggregated as quantiles; and some histograms. Graphical conventions that generate minimal artifacts include scatterplots with a best-fit line that depict (y vs. (x measures (self-assessed competence vs. measured competence plotted by individual participant scores, and (y vs. (x scatterplots of collective average measures of all participants plotted item-by-item. This last graphic convention attenuates noise and improves the definition of the signal. To provide relevant comparisons across varied graphical conventions, we use a single dataset derived from paired measures of 1154 participants' self-assessed competence and demonstrated competence in science literacy. Our results show that different numerical approaches employed in investigating and describing self-assessment accuracy are not equally valid. By modeling this dataset with random numbers, we show how recognizing the varied expressions of randomness in self-assessment data can improve the validity of numeracy-based descriptions of self-assessment.
Sepúlveda, Nuno
2013-02-26
Background: The advent of next generation sequencing technology has accelerated efforts to map and catalogue copy number variation (CNV) in genomes of important micro-organisms for public health. A typical analysis of the sequence data involves mapping reads onto a reference genome, calculating the respective coverage, and detecting regions with too-low or too-high coverage (deletions and amplifications, respectively). Current CNV detection methods rely on statistical assumptions (e.g., a Poisson model) that may not hold in general, or require fine-tuning the underlying algorithms to detect known hits. We propose a new CNV detection methodology based on two Poisson hierarchical models, the Poisson-Gamma and Poisson-Lognormal, with the advantage of being sufficiently flexible to describe different data patterns, whilst robust against deviations from the often assumed Poisson model.Results: Using sequence coverage data of 7 Plasmodium falciparum malaria genomes (3D7 reference strain, HB3, DD2, 7G8, GB4, OX005, and OX006), we showed that empirical coverage distributions are intrinsically asymmetric and overdispersed in relation to the Poisson model. We also demonstrated a low baseline false positive rate for the proposed methodology using 3D7 resequencing data and simulation. When applied to the non-reference isolate data, our approach detected known CNV hits, including an amplification of the PfMDR1 locus in DD2 and a large deletion in the CLAG3.2 gene in GB4, and putative novel CNV regions. When compared to the recently available FREEC and cn.MOPS approaches, our findings were more concordant with putative hits from the highest quality array data for the 7G8 and GB4 isolates.Conclusions: In summary, the proposed methodology brings an increase in flexibility, robustness, accuracy and statistical rigour to CNV detection using sequence coverage data. 2013 Seplveda et al.; licensee BioMed Central Ltd.
Variations in CCL3L gene cluster sequence and non-specific gene copy numbers
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Edberg Jeffrey C
2010-03-01
Full Text Available Abstract Background Copy number variations (CNVs of the gene CC chemokine ligand 3-like1 (CCL3L1 have been implicated in HIV-1 susceptibility, but the association has been inconsistent. CCL3L1 shares homology with a cluster of genes localized to chromosome 17q12, namely CCL3, CCL3L2, and, CCL3L3. These genes are involved in host defense and inflammatory processes. Several CNV assays have been developed for the CCL3L1 gene. Findings Through pairwise and multiple alignments of these genes, we have shown that the homology between these genes ranges from 50% to 99% in complete gene sequences and from 70-100% in the exonic regions, with CCL3L1 and CCL3L3 being identical. By use of MEGA 4 and BioEdit, we aligned sense primers, anti-sense primers, and probes used in several previously described assays against pre-multiple alignments of all four chemokine genes. Each set of probes and primers aligned and matched with overlapping sequences in at least two of the four genes, indicating that previously utilized RT-PCR based CNV assays are not specific for only CCL3L1. The four available assays measured median copies of 2 and 3-4 in European and African American, respectively. The concordance between the assays ranged from 0.44-0.83 suggesting individual discordant calls and inconsistencies with the assays from the expected gene coverage from the known sequence. Conclusions This indicates that some of the inconsistencies in the association studies could be due to assays that provide heterogenous results. Sequence information to determine CNV of the three genes separately would allow to test whether their association with the pathogenesis of a human disease or phenotype is affected by an individual gene or by a combination of these genes.
Sepúlveda, Nuno; Campino, Susana G; Assefa, Samuel A; Sutherland, Colin J; Pain, Arnab; Clark, Taane G
2013-02-26
The advent of next generation sequencing technology has accelerated efforts to map and catalogue copy number variation (CNV) in genomes of important micro-organisms for public health. A typical analysis of the sequence data involves mapping reads onto a reference genome, calculating the respective coverage, and detecting regions with too-low or too-high coverage (deletions and amplifications, respectively). Current CNV detection methods rely on statistical assumptions (e.g., a Poisson model) that may not hold in general, or require fine-tuning the underlying algorithms to detect known hits. We propose a new CNV detection methodology based on two Poisson hierarchical models, the Poisson-Gamma and Poisson-Lognormal, with the advantage of being sufficiently flexible to describe different data patterns, whilst robust against deviations from the often assumed Poisson model. Using sequence coverage data of 7 Plasmodium falciparum malaria genomes (3D7 reference strain, HB3, DD2, 7G8, GB4, OX005, and OX006), we showed that empirical coverage distributions are intrinsically asymmetric and overdispersed in relation to the Poisson model. We also demonstrated a low baseline false positive rate for the proposed methodology using 3D7 resequencing data and simulation. When applied to the non-reference isolate data, our approach detected known CNV hits, including an amplification of the PfMDR1 locus in DD2 and a large deletion in the CLAG3.2 gene in GB4, and putative novel CNV regions. When compared to the recently available FREEC and cn.MOPS approaches, our findings were more concordant with putative hits from the highest quality array data for the 7G8 and GB4 isolates. In summary, the proposed methodology brings an increase in flexibility, robustness, accuracy and statistical rigour to CNV detection using sequence coverage data.
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Cornejo Diaz, N.; Vergara Gil, A. [Centre for Radiological Protection and Higiene, P.O. Box 6195, Habana (Cuba); Jurado Vargas, M. [Physics Department, University of Extremadura, 06071 Badajoz (Spain)], E-mail: mjv@unex.es
2010-03-15
The Monte Carlo method has become a valuable numerical laboratory framework in which to simulate complex physical systems. It is based on the generation of pseudo-random number sequences by numerical algorithms called random generators. In this work we assessed the suitability of different well-known random number generators for the simulation of gamma-ray spectrometry systems during efficiency calibrations. The assessment was carried out in two stages. The generators considered (Delphi's linear congruential, mersenne twister, XorShift, multiplier with carry, universal virtual array, and non-periodic logistic map based generator) were first evaluated with different statistical empirical tests, including moments, correlations, uniformity, independence of terms and the DIEHARD battery of tests. In a second step, an application-specific test was conducted by implementing the generators in our Monte Carlo program DETEFF and comparing the results obtained with them. The calculations were performed with two different CPUs, for a typical HpGe detector and a water sample in Marinelli geometry, with gamma-rays between 59 and 1800 keV. For the Non-periodic Logistic Map based generator, dependence of the most significant bits was evident. This explains the bias, in excess of 5%, of the efficiency values obtained with this generator. The results of the application-specific assessment and the statistical performance of the other algorithms studied indicate their suitability for the Monte Carlo simulation of gamma-ray spectrometry systems for efficiency calculations.
Sequences of ground states and classification of frustration in odd-numbered antiferromagnetic rings
Florek, Wojciech; Antkowiak, Michał; Kamieniarz, Grzegorz
2016-12-01
The sequences of ground states in frustrated antiferromagnetic rings with odd number of local spins characterized by a single bond defect or by arbitrary uniform couplings to an additional spin located at the center are determined. The sequences provide firm constraints on the total ground-state quantum numbers, which are more stringent than those arising from the Lieb-Mattis theorem for bipartite quantum spin systems. Apart from their theoretical importance, they suggest the possibility of tailoring a given class of the molecular nanomagnets with desired ground-state properties by tuning the relevant couplings. In particular, they predict the spin S =1 /2 ground state for the centered rings composed of the half-integer spins with approximately uniform interactions. They confirm the applicability of the recent classification of spin frustration in both types of molecular nanomagnets. The classification is also discussed in the classical limit for the first class of the rings, providing a direct picture of frustration types. The Lieb-Mattis energy-level ordering and an analog of the Landé band, i.e., the energy spectra properties simplifying the characterization of the rings using the bulk magnetic or NMR measurements, are briefly discussed.
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Hamdan Amer C.
2004-01-01
Full Text Available OBJECTIVE: To evaluate the performance of adult young subjects in a Random Number Generation (RNG task by controlling the response speed (RS. METHOD: Sixty-nine university students of both sexes took part in the experiment (25.05 ± 6.71 year-old. Participants were alloted into 3 groups which differed in RS rates to generate numbers: 1, 2 and 4 seconds to generate each number. A digital metronomer was used to control RS. Participants were asked to generate 100 numbers. The responses were mensured through Evans's RNG Index. RESULTS: There were statistically significant differences among the groups [F (3, 68 = 7.120; p < .05]. Differences were localized between 1 and 2 seconds (p = 0.004 and between 1 and 4 seconds (p = 0.006. No differences were observed between 2 and 4 seconds (p = 0.985. CONCLUSION: The present results suggest that the response speed in production of random numbers influences the performance of the Random Numbers Generation task.
Yushkevich, A. A.; Chitashvili, R. Ya
1982-12-01
CONTENTSIntroduction Chapter I. Foundations of the general theory of controlled random sequences and Markov chains with the expected reward criterion § 1. Controlled random sequences, Markov chains, and models § 2. Necessary and sufficient conditions for optimality § 3. The Bellman equation for the value function and the existence of (ε-) optimal strategies Chapter II. Some problems in the theory of controlled homogeneous Markov chains § 4. Description of the solutions of the Bellman equation, a characterization of the value function, and the Bellman operator § 5. Sufficiency of stationary strategies in homogeneous Markov models § 6. The lexicographic Bellman equation References
Bosch, Holger; Steinkamp, Fiona; Boller, Emil
2006-01-01
Seance-room and other large-scale psychokinetic phenomena have fascinated humankind for decades. Experimental research has reduced these phenomena to attempts to influence (a) the fall of dice and, later, (b) the output of random number generators (RNGs). The meta-analysis combined 380 studies that assessed whether RNG output correlated with human…
On the variance of the number of real roots of a random trigonometric polynomial
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K. Farahmand
1990-01-01
Full Text Available This paper provides an upper estimate for the variance of the number of real zeros of the random trigonometric polynomial g1cosθ+g2cos2θ+…+gncosnθ. The coefficients gi(i=1,2,…,n are assumed independent and normally distributed with mean zero and variance one.
Oomens, W.; Maes, J.H.R.; Hasselman, F.W.; Egger, J.I.M.
2015-01-01
The concept of executive functions plays a prominent role in contemporary experimental and clinical studies on cognition. One paradigm used in this framework is the random number generation (RNG) task, the execution of which demands aspects of executive functioning, specifically inhibition and
Pseudo-Random Number Generators for Vector Processors and Multicore Processors
DEFF Research Database (Denmark)
Fog, Agner
2015-01-01
Large scale Monte Carlo applications need a good pseudo-random number generator capable of utilizing both the vector processing capabilities and multiprocessing capabilities of modern computers in order to get the maximum performance. The requirements for such a generator are discussed. New ways ...
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Аndriy V. Sadchenko
2015-12-01
Full Text Available Digital television systems need to ensure that all digital signals processing operations are performed simultaneously and consistently. Frame synchronization dictated by the need to match phases of transmitter and receiver so that it would be possible to identify the start of a frame. As a frame synchronization signals are often used long length binary sequence with good aperiodic autocorrelation function. Aim: This work is dedicated to the development of the algorithm of random length sequences synthesis. Materials and Methods: The paper provides a comparative analysis of the known sequences, which can be used at present as synchronization ones, revealed their advantages and disadvantages. This work proposes the algorithm for the synthesis of binary synchronization sequences of random length with good autocorrelation properties based on noise generator with a uniform distribution law of probabilities. A "white noise" semiconductor generator is proposed to use as the initial material for the synthesis of binary sequences with desired properties. Results: The statistical analysis of the initial implementations of the "white noise" and synthesized sequences for frame synchronization of digital television is conducted. The comparative analysis of the synthesized sequences with known ones was carried out. The results show the benefits of obtained sequences in compare with known ones. The performed simulations confirm the obtained results. Conclusions: Thus, the search algorithm of binary synchronization sequences with desired autocorrelation properties received. According to this algorithm, the sequence can be longer in length and without length limitations. The received sync sequence can be used for frame synchronization in modern digital communication systems that will increase their efficiency and noise immunity.
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Jo Nishino
2013-01-01
Full Text Available There has been recent success in identifying disease-causing variants in Mendelian disorders by exome sequencing followed by simple filtering techniques. Studies generally assume complete or high penetrance. However, there are likely many failed and unpublished studies due in part to incomplete penetrance or phenocopy. In this study, the expected number of candidate single-nucleotide variants (SNVs in exome data for autosomal dominant or recessive Mendelian disorders was investigated under the assumption of “no genetic heterogeneity.” All variants were assumed to be under the “null model,” and sample allele frequencies were modeled using a standard population genetics theory. To investigate the properties of pedigree data, full-sibs were considered in addition to unrelated individuals. In both cases, particularly regarding full-sibs, the number of SNVs remained very high without controls. The high efficacy of controls was also confirmed. When controls were used with a relatively large total sample size (e.g., N=20, 50, filtering incorporating of incomplete penetrance and phenocopy efficiently reduced the number of candidate SNVs. This suggests that filtering is useful when an assumption of no “genetic heterogeneity” is appropriate and could provide general guidelines for sample size determination.
Nishino, Jo; Mano, Shuhei
2013-01-01
There has been recent success in identifying disease-causing variants in Mendelian disorders by exome sequencing followed by simple filtering techniques. Studies generally assume complete or high penetrance. However, there are likely many failed and unpublished studies due in part to incomplete penetrance or phenocopy. In this study, the expected number of candidate single-nucleotide variants (SNVs) in exome data for autosomal dominant or recessive Mendelian disorders was investigated under the assumption of "no genetic heterogeneity." All variants were assumed to be under the "null model," and sample allele frequencies were modeled using a standard population genetics theory. To investigate the properties of pedigree data, full-sibs were considered in addition to unrelated individuals. In both cases, particularly regarding full-sibs, the number of SNVs remained very high without controls. The high efficacy of controls was also confirmed. When controls were used with a relatively large total sample size (e.g., N = 20, 50), filtering incorporating of incomplete penetrance and phenocopy efficiently reduced the number of candidate SNVs. This suggests that filtering is useful when an assumption of no "genetic heterogeneity" is appropriate and could provide general guidelines for sample size determination.
DEEPre: sequence-based enzyme EC number prediction by deep learning
Li, Yu
2017-10-20
Annotation of enzyme function has a broad range of applications, such as metagenomics, industrial biotechnology, and diagnosis of enzyme deficiency-caused diseases. However, the time and resource required make it prohibitively expensive to experimentally determine the function of every enzyme. Therefore, computational enzyme function prediction has become increasingly important. In this paper, we develop such an approach, determining the enzyme function by predicting the Enzyme Commission number.We propose an end-to-end feature selection and classification model training approach, as well as an automatic and robust feature dimensionality uniformization method, DEEPre, in the field of enzyme function prediction. Instead of extracting manuallycrafted features from enzyme sequences, our model takes the raw sequence encoding as inputs, extracting convolutional and sequential features from the raw encoding based on the classification result to directly improve the prediction performance. The thorough cross-fold validation experiments conducted on two large-scale datasets show that DEEPre improves the prediction performance over the previous state-of-the-art methods. In addition, our server outperforms five other servers in determining the main class of enzymes on a separate low-homology dataset. Two case studies demonstrate DEEPre\\'s ability to capture the functional difference of enzyme isoforms.The server could be accessed freely at http://www.cbrc.kaust.edu.sa/DEEPre.
DEEPre: sequence-based enzyme EC number prediction by deep learning.
Li, Yu; Wang, Sheng; Umarov, Ramzan; Xie, Bingqing; Fan, Ming; Li, Lihua; Gao, Xin
2017-10-23
Annotation of enzyme function has a broad range of applications, such as metagenomics, industrial biotechnology, and diagnosis of enzyme deficiency-caused diseases. However, the time and resource required make it prohibitively expensive to experimentally determine the function of every enzyme. Therefore, computational enzyme function prediction has become increasingly important. In this paper, we develop such an approach, determining the enzyme function by predicting the Enzyme Commission number. We propose an end-to-end feature selection and classification model training approach, as well as an automatic and robust feature dimensionality uniformization method, DEEPre, in the field of enzyme function prediction. Instead of extracting manuallycrafted features from enzyme sequences, our model takes the raw sequence encoding as inputs, extracting convolutional and sequential features from the raw encoding based on the classification result to directly improve the prediction performance. The thorough cross-fold validation experiments conducted on two large-scale datasets show that DEEPre improves the prediction performance over the previous state-of-the-art methods. In addition, our server outperforms five other servers in determining the main class of enzymes on a separate low-homology dataset. Two case studies demonstrate DEEPre's ability to capture the functional difference of enzyme isoforms. The server could be accessed freely at http://www.cbrc.kaust.edu.sa/DEEPre.
Rampášek, Ladislav; Arbabi, Aryan; Brudno, Michael
2014-06-15
The past several years have seen the development of methodologies to identify genomic variation within a fetus through the non-invasive sequencing of maternal blood plasma. These methods are based on the observation that maternal plasma contains a fraction of DNA (typically 5-15%) originating from the fetus, and such methodologies have already been used for the detection of whole-chromosome events (aneuploidies), and to a more limited extent for smaller (typically several megabases long) copy number variants (CNVs). Here we present a probabilistic method for non-invasive analysis of de novo CNVs in fetal genome based on maternal plasma sequencing. Our novel method combines three types of information within a unified Hidden Markov Model: the imbalance of allelic ratios at SNP positions, the use of parental genotypes to phase nearby SNPs and depth of coverage to better differentiate between various types of CNVs and improve precision. Our simulation results, based on in silico introduction of novel CNVs into plasma samples with 13% fetal DNA concentration, demonstrate a sensitivity of 90% for CNVs >400 kb (with 13 calls in an unaffected genome), and 40% for 50-400 kb CNVs (with 108 calls in an unaffected genome). Implementation of our model and data simulation method is available at http://github.com/compbio-UofT/fCNV. © The Author 2014. Published by Oxford University Press.
Hansen, Marie J; Rasmussen, Nana Ø; Chung, Grace
2008-01-01
We have developed a method for extracting the number of trial participants from abstracts describing randomized controlled trials (RCTs); the number of trial participants may be an indication of the reliability of the trial. The method depends on statistical natural language processing. The number of interest was determined by a binary supervised classification based on a support vector machine algorithm. The method was trialled on 223 abstracts in which the number of trial participants was identified manually to act as a gold standard. Automatic extraction resulted in 2 false-positive and 19 false-negative classifications. The algorithm was capable of extracting the number of trial participants with an accuracy of 97% and an F-measure of 0.84. The algorithm may improve the selection of relevant articles in regard to question-answering, and hence may assist in decision-making.
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Qi, Shuyan [Department of Chemical Engineering, Department of Chemistry, and Materials Science Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720 (United States); Chakraborty, Arup K. [Department of Chemical Engineering, Department of Chemistry, and Materials Science Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720 (United States)
2000-01-15
We derive a Landau free energy functional for polymeric mixtures containing components with different sequence statistics. We then apply this general field theory to two mixtures that belong to the Ising universality class: mixtures of two different linear random copolymers, and ternary systems of linear random copolymers and two homopolymers. We discuss the instability conditions for the homogeneous state of these mixtures, and calculate the structure factors for different components in the homogeneous state. The structure factors show interesting features which can directly be compared with scattering experiments carried out with selectively deuterated samples. We also work out the eigenmodes representing the least stable concentration fluctuations for these mixtures. The nature of these concentration fluctuations provides information regarding the ordered phases and the kinetic pathways that lead to them. We find various demixing modes for different characteristics of the two mixtures (e.g., average compositions, statistical correlation lengths, and volume fractions). (c) 2000 American Institute of Physics.
Covariance of the number of real zeros of a random trigonometric polynomial
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K. Farahmand
2006-01-01
Full Text Available For random coefficients aj and bj we consider a random trigonometric polynomial defined as Tn(θ=∑j=0n{ajcosjθ+bjsinjθ}. The expected number of real zeros of Tn(θ in the interval (0,2π can be easily obtained. In this note we show that this number is in fact n/3. However the variance of the above number is not known. This note presents a method which leads to the asymptotic value for the covariance of the number of real zeros of the above polynomial in intervals (0,π and (π,2π. It can be seen that our method in fact remains valid to obtain the result for any two disjoint intervals. The applicability of our method to the classical random trigonometric polynomial, defined as Pn(θ=∑j=0naj(ωcosjθ, is also discussed. Tn(θ has the advantage on Pn(θ of being stationary, with respect to θ, for which, therefore, a more advanced method developed could be used to yield the results.
Directory of Open Access Journals (Sweden)
Elena Hilario
Full Text Available Genotyping by sequencing (GBS is a restriction enzyme based targeted approach developed to reduce the genome complexity and discover genetic markers when a priori sequence information is unavailable. Sufficient coverage at each locus is essential to distinguish heterozygous from homozygous sites accurately. The number of GBS samples able to be pooled in one sequencing lane is limited by the number of restriction sites present in the genome and the read depth required at each site per sample for accurate calling of single-nucleotide polymorphisms. Loci bias was observed using a slight modification of the Elshire et al.some restriction enzyme sites were represented in higher proportions while others were poorly represented or absent. This bias could be due to the quality of genomic DNA, the endonuclease and ligase reaction efficiency, the distance between restriction sites, the preferential amplification of small library restriction fragments, or bias towards cluster formation of small amplicons during the sequencing process. To overcome these issues, we have developed a GBS method based on randomly tagging genomic DNA (rtGBS. By randomly landing on the genome, we can, with less bias, find restriction sites that are far apart, and undetected by the standard GBS (stdGBS method. The study comprises two types of biological replicates: six different kiwifruit plants and two independent DNA extractions per plant; and three types of technical replicates: four samples of each DNA extraction, stdGBS vs. rtGBS methods, and two independent library amplifications, each sequenced in separate lanes. A statistically significant unbiased distribution of restriction fragment size by rtGBS showed that this method targeted 49% (39,145 of BamH I sites shared with the reference genome, compared to only 14% (11,513 by stdGBS.
LPEseq: Local-Pooled-Error Test for RNA Sequencing Experiments with a Small Number of Replicates.
Gim, Jungsoo; Won, Sungho; Park, Taesung
2016-01-01
RNA-Sequencing (RNA-Seq) provides valuable information for characterizing the molecular nature of the cells, in particular, identification of differentially expressed transcripts on a genome-wide scale. Unfortunately, cost and limited specimen availability often lead to studies with small sample sizes, and hypothesis testing on differential expression between classes with a small number of samples is generally limited. The problem is especially challenging when only one sample per each class exists. In this case, only a few methods among many that have been developed are applicable for identifying differentially expressed transcripts. Thus, the aim of this study was to develop a method able to accurately test differential expression with a limited number of samples, in particular non-replicated samples. We propose a local-pooled-error method for RNA-Seq data (LPEseq) to account for non-replicated samples in the analysis of differential expression. Our LPEseq method extends the existing LPE method, which was proposed for microarray data, to allow examination of non-replicated RNA-Seq experiments. We demonstrated the validity of the LPEseq method using both real and simulated datasets. By comparing the results obtained using the LPEseq method with those obtained from other methods, we found that the LPEseq method outperformed the others for non-replicated datasets, and showed a similar performance with replicated samples; LPEseq consistently showed high true discovery rate while not increasing the rate of false positives regardless of the number of samples. Our proposed LPEseq method can be effectively used to conduct differential expression analysis as a preliminary design step or for investigation of a rare specimen, for which a limited number of samples is available.
Gromko, Joyce Eastlund; Hansen, Dee; Tortora, Anne Halloran; Higgins, Daniel; Boccia, Eric
2009-01-01
The purpose of this study was to determine whether children's recall of tones, numbers, and words was supported by a common temporal sequencing mechanism; whether children's patterns of memory for tones, numbers, and nonsense words were the same despite differences in symbol systems; and whether children's recall of tones, numbers, and nonsense…
Wang, Yonggang; Hui, Cong; Liu, Chong; Xu, Chao
2016-04-01
The contribution of this paper is proposing a new entropy extraction mechanism based on sampling phase jitter in ring oscillators to make a high throughput true random number generator in a field programmable gate array (FPGA) practical. Starting from experimental observation and analysis of the entropy source in FPGA, a multi-phase sampling method is exploited to harvest the clock jitter with a maximum entropy and fast sampling speed. This parametrized design is implemented in a Xilinx Artix-7 FPGA, where the carry chains in the FPGA are explored to realize the precise phase shifting. The generator circuit is simple and resource-saving, so that multiple generation channels can run in parallel to scale the output throughput for specific applications. The prototype integrates 64 circuit units in the FPGA to provide a total output throughput of 7.68 Gbps, which meets the requirement of current high-speed quantum key distribution systems. The randomness evaluation, as well as its robustness to ambient temperature, confirms that the new method in a purely digital fashion can provide high-speed high-quality random bit sequences for a variety of embedded applications.
Wave-number-frequency spectrum for turbulence from a random sweeping hypothesis with mean flow.
Wilczek, M; Narita, Y
2012-12-01
We derive the energy spectrum in wave-number-frequency space for turbulent flows based on Kraichnan's idealized random sweeping hypothesis with additional mean flow, which yields the instantaneous energy spectrum multiplied by a Gaussian frequency distribution. The model spectrum has two adjustable parameters, the mean flow velocity and the sweeping velocity, and has the property that the power-law index of the wave-number spectrum translates to the frequency spectrum, invariant for arbitrary choices of the mean velocity and sweeping velocity. The model spectrum incorporates both Taylor's frozen-in flow approximation and the random sweeping approximation in a natural way and can be used to distinguish between these two effects when applied to real time-resolved multipoint turbulence data. Evaluated in real space, its properties with respect to space-time velocity correlations are discussed, and a comparison to the recently introduced elliptic model is drawn.
Generating log-normally distributed random numbers by using the Ziggurat algorithm
Energy Technology Data Exchange (ETDEWEB)
Choi, Jong Soo [KINS, Daejeon (Korea, Republic of)
2016-05-15
Uncertainty analyses are usually based on the Monte Carlo method. Using an efficient random number generator(RNG) is a key element in success of Monte Carlo simulations. Log-normal distributed variates are very typical in NPP PSAs. This paper proposes an approach to generate log normally distributed variates based on the Ziggurat algorithm and evaluates the efficiency of the proposed Ziggurat RNG. The proposed RNG can be helpful to improve the uncertainty analysis of NPP PSAs. This paper focuses on evaluating the efficiency of the Ziggurat algorithm from a NPP PSA point of view. From this study, we can draw the following conclusions. - The Ziggurat algorithm is one of perfect random number generators to product normal distributed variates. - The Ziggurat algorithm is computationally much faster than the most commonly used method, Marsaglia polar method.
Oracle inequalities for SVMs that are based on random entropy numbers
Energy Technology Data Exchange (ETDEWEB)
Steinwart, Ingo [Los Alamos National Laboratory
2009-01-01
In this paper we present a new technique for bounding local Rademacher averages of function classes induced by a loss function and a reproducing kernel Hilbert space (RKHS). At the heart of this technique lies the observation that certain expectations of random entropy numbers can be bounded by the eigenvalues of the integral operator associated to the RKHS. We then work out the details of the new technique by establishing two new oracle inequalities for SVMs, which complement and generalize orevious results.
On the number of common sites visited by N random walkers
Turban, L
2016-01-01
Majumdar and Tamm [Phys. Rev. E 86 021135 (2012), arXiv:1206.6184] recently obtained analytical expressions for the mean number of common sites W_N(t) visited up to time t by N independent random walkers starting from the origin of a d-dimensional lattice. In this short note I show how the different regimes and the corresponding asymptotic power laws can be retrieved using the notion of fractal intersection.
Concurrent Generation of Pseudo Random Numbers with LFSR of Fibonacci and Galois Type
Emina I. Milovanović; Stojčev, Mile K.; Igor Ž. Milovanović; Tatjana R. Nikolić; Zoran Stamenković
2016-01-01
We have considered implementation of parallel test pattern generator based on a linear feedback shift register (LFSR) with multiple outputs used as a building block in built-in-self-test (BIST) design within SoC. The proposed design can drive several circuits under test (CUT) simultaneously. The mathematical procedure for concurrent pseudo random number (PRN) generation is described. We have implemented LFSRs that generate two and three PRNs in FPGA and ASIC technology. The design was tested ...
Boonsathorn, Wasita; Charoen, Danuvasin; Dryver, Arthur L.
2014-01-01
E-Learning brings access to a powerful but often overlooked teaching tool: random number generation. Using random number generation, a practically infinite number of quantitative problem-solution sets can be created. In addition, within the e-learning context, in the spirit of the mastery of learning, it is possible to assign online quantitative…
Random-effects meta-analysis: the number of studies matters.
Guolo, Annamaria; Varin, Cristiano
2017-06-01
This paper investigates the impact of the number of studies on meta-analysis and meta-regression within the random-effects model framework. It is frequently neglected that inference in random-effects models requires a substantial number of studies included in meta-analysis to guarantee reliable conclusions. Several authors warn about the risk of inaccurate results of the traditional DerSimonian and Laird approach especially in the common case of meta-analysis involving a limited number of studies. This paper presents a selection of likelihood and non-likelihood methods for inference in meta-analysis proposed to overcome the limitations of the DerSimonian and Laird procedure, with a focus on the effect of the number of studies. The applicability and the performance of the methods are investigated in terms of Type I error rates and empirical power to detect effects, according to scenarios of practical interest. Simulation studies and applications to real meta-analyses highlight that it is not possible to identify an approach uniformly superior to alternatives. The overall recommendation is to avoid the DerSimonian and Laird method when the number of meta-analysis studies is modest and prefer a more comprehensive procedure that compares alternative inferential approaches. R code for meta-analysis according to all of the inferential methods examined in the paper is provided.
Human PTCHD3 nulls: rare copy number and sequence variants suggest a non-essential gene
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Lionel Anath C
2011-03-01
Full Text Available Abstract Background Copy number variations (CNVs can contribute to variable degrees of fitness and/or disease predisposition. Recent studies show that at least 1% of any given genome is copy number variable when compared to the human reference sequence assembly. Homozygous deletions (or CNV nulls that are found in the normal population are of particular interest because they may serve to define non-essential genes in human biology. Results In a genomic screen investigating CNV in Autism Spectrum Disorders (ASDs we detected a heterozygous deletion on chromosome 10p12.1, spanning the Patched-domain containing 3 (PTCHD3 gene, at a frequency of ~1.4% (6/427. This finding seemed interesting, given recent discoveries on the role of another Patched-domain containing gene (PTCHD1 in ASD. Screening of another 177 ASD probands yielded two additional heterozygous deletions bringing the frequency to 1.3% (8/604. The deletion was found at a frequency of ~0.73% (27/3,695 in combined control population from North America and Northern Europe predominately of European ancestry. Screening of the human genome diversity panel (HGDP-CEPH covering worldwide populations yielded deletions in 7/1,043 unrelated individuals and those detected were confined to individuals of European/Mediterranean/Middle Eastern ancestry. Breakpoint mapping yielded an identical 102,624 bp deletion in all cases and controls tested, suggesting a common ancestral event. Interestingly, this CNV occurs at a break of synteny between humans and mouse. Considering all data, however, no significant association of these rare PTCHD3 deletions with ASD was observed. Notwithstanding, our RNA expression studies detected PTCHD3 in several tissues, and a novel shorter isoform for PTCHD3 was characterized. Expression in transfected COS-7 cells showed PTCHD3 isoforms colocalize with calnexin in the endoplasmic reticulum. The presence of a patched (Ptc domain suggested a role for PTCHD3 in various biological
Zhmurov, A; Rybnikov, K; Kholodov, Y; Barsegov, V
2011-05-12
The use of graphics processing units (GPUs) in simulation applications offers a significant speed gain as compared to computations on central processing units (CPUs). Many simulation methods require a large number of independent random variables generated at each step. We present two approaches for implementation of random number generators (RNGs) on a GPU. In the one-RNG-per-thread approach, one RNG produces a stream of random numbers in each thread of execution, whereas the one-RNG-for-all-threads method builds on the ability of different threads to communicate, thus, sharing random seeds across an entire GPU device. We used these approaches to implement Ran2, Hybrid Taus, and Lagged Fibonacci algorithms on a GPU. We profiled the performance of these generators in terms of the computational time, memory usage, and the speedup factor (CPU time/GPU time). These generators have been incorporated into the program for Langevin simulations of biomolecules fully implemented on the GPU. The ∼250-fold computational speedup on the GPU allowed us to carry out single-molecule dynamic force measurements in silico to explore the mechanical properties of the bacteriophage HK97 in the experimental subsecond time scale. We found that the nanomechanical response of HK97 depends on the conditions of force application, including the rate of change and geometry of the mechanical perturbation. Hence, using the GPU-based implementation of RNGs, presented here, in conjunction with Langevin simulations, makes it possible to directly compare the results of dynamic force measurements in vitro and in silico.
Liu, Hongtai; Gao, Ya; Hu, Zhiyang; Lin, Linhua; Yin, Xuyang; Wang, Jun; Chen, Dayang; Chen, Fang; Jiang, Hui; Ren, Jinghui; Wang, Wei
2016-01-01
The aim of this study was to assess the performance of noninvasively prenatal testing (NIPT) for fetal copy number variants (CNVs) in clinical samples, using a whole-genome sequencing method. A total of 919 archived maternal plasma samples with karyotyping/microarray results, including 33 CNVs samples and 886 normal samples from September 1, 2011 to May 31, 2013, were enrolled in this study. The samples were randomly rearranged and blindly sequenced by low-coverage (about 7M reads) whole-genome sequencing of plasma DNA. Fetal CNVs were detected by Fetal Copy-number Analysis through Maternal Plasma Sequencing (FCAPS) to compare to the karyotyping/microarray results. Sensitivity, specificity and were evaluated. 33 samples with deletions/duplications ranging from 1 to 129 Mb were detected with the consistent CNV size and location to karyotyping/microarray results in the study. Ten false positive results and two false negative results were obtained. The sensitivity and specificity of detection deletions/duplications were 84.21% and 98.42%, respectively. Whole-genome sequencing-based NIPT has high performance in detecting genome-wide CNVs, in particular >10Mb CNVs using the current FCAPS algorithm. It is possible to implement the current method in NIPT to prenatally screening for fetal CNVs.
Directory of Open Access Journals (Sweden)
Hongtai Liu
Full Text Available The aim of this study was to assess the performance of noninvasively prenatal testing (NIPT for fetal copy number variants (CNVs in clinical samples, using a whole-genome sequencing method.A total of 919 archived maternal plasma samples with karyotyping/microarray results, including 33 CNVs samples and 886 normal samples from September 1, 2011 to May 31, 2013, were enrolled in this study. The samples were randomly rearranged and blindly sequenced by low-coverage (about 7M reads whole-genome sequencing of plasma DNA. Fetal CNVs were detected by Fetal Copy-number Analysis through Maternal Plasma Sequencing (FCAPS to compare to the karyotyping/microarray results. Sensitivity, specificity and were evaluated.33 samples with deletions/duplications ranging from 1 to 129 Mb were detected with the consistent CNV size and location to karyotyping/microarray results in the study. Ten false positive results and two false negative results were obtained. The sensitivity and specificity of detection deletions/duplications were 84.21% and 98.42%, respectively.Whole-genome sequencing-based NIPT has high performance in detecting genome-wide CNVs, in particular >10Mb CNVs using the current FCAPS algorithm. It is possible to implement the current method in NIPT to prenatally screening for fetal CNVs.
PartTree: an algorithm to build an approximate tree from a large number of unaligned sequences.
Katoh, Kazutaka; Toh, Hiroyuki
2007-02-01
To construct a multiple sequence alignment (MSA) of a large number (> approximately 10,000) of sequences, the calculation of a guide tree with a complexity of O(N2) to O(N3), where N is the number of sequences, is the most time-consuming process. To overcome this limitation, we have developed an approximate algorithm, PartTree, to construct a guide tree with an average time complexity of O(N log N). The new MSA method with the PartTree algorithm can align approximately 60,000 sequences in several minutes on a standard desktop computer. The loss of accuracy in MSA caused by this approximation was estimated to be several percent in benchmark tests using Pfam. The present algorithm has been implemented in the MAFFT sequence alignment package (http://align.bmr.kyushu-u.ac.jp/mafft/software/). Supplementary information is available at Bioinformatics online.
Application of random number generators in genetic algorithms to improve rainfall-runoff modelling
Chlumecký, Martin; Buchtele, Josef; Richta, Karel
2017-10-01
The efficient calibration of rainfall-runoff models is a difficult issue, even for experienced hydrologists. Therefore, fast and high-quality model calibration is a valuable improvement. This paper describes a novel methodology and software for the optimisation of a rainfall-runoff modelling using a genetic algorithm (GA) with a newly prepared concept of a random number generator (HRNG), which is the core of the optimisation. The GA estimates model parameters using evolutionary principles, which requires a quality number generator. The new HRNG generates random numbers based on hydrological information and it provides better numbers compared to pure software generators. The GA enhances the model calibration very well and the goal is to optimise the calibration of the model with a minimum of user interaction. This article focuses on improving the internal structure of the GA, which is shielded from the user. The results that we obtained indicate that the HRNG provides a stable trend in the output quality of the model, despite various configurations of the GA. In contrast to previous research, the HRNG speeds up the calibration of the model and offers an improvement of rainfall-runoff modelling.
Tolentino, Jerlyn C.; Pirogovsky, Eva; Luu, Trinh; Toner, Chelsea K.; Gilbert, Paul E.
2012-01-01
Two experiments tested the effect of temporal interference on order memory for fixed and random sequences in young adults and nondemented older adults. The results demonstrate that temporal order memory for fixed and random sequences is impaired in nondemented older adults, particularly when temporal interference is high. However, temporal order…
Novitsky, Vlad; Moyo, Sikhulile; Lei, Quanhong; DeGruttola, Victor; Essex, M
2015-05-01
To improve the methodology of HIV cluster analysis, we addressed how analysis of HIV clustering is associated with parameters that can affect the outcome of viral clustering. The extent of HIV clustering and tree certainty was compared between 401 HIV-1C near full-length genome sequences and subgenomic regions retrieved from the LANL HIV Database. Sliding window analysis was based on 99 windows of 1,000 bp and 45 windows of 2,000 bp. Potential associations between the extent of HIV clustering and sequence length and the number of variable and informative sites were evaluated. The near full-length genome HIV sequences showed the highest extent of HIV clustering and the highest tree certainty. At the bootstrap threshold of 0.80 in maximum likelihood (ML) analysis, 58.9% of near full-length HIV-1C sequences but only 15.5% of partial pol sequences (ViroSeq) were found in clusters. Among HIV-1 structural genes, pol showed the highest extent of clustering (38.9% at a bootstrap threshold of 0.80), although it was significantly lower than in the near full-length genome sequences. The extent of HIV clustering was significantly higher for sliding windows of 2,000 bp than 1,000 bp. We found a strong association between the sequence length and proportion of HIV sequences in clusters, and a moderate association between the number of variable and informative sites and the proportion of HIV sequences in clusters. In HIV cluster analysis, the extent of detectable HIV clustering is directly associated with the length of viral sequences used, as well as the number of variable and informative sites. Near full-length genome sequences could provide the most informative HIV cluster analysis. Selected subgenomic regions with a high extent of HIV clustering and high tree certainty could also be considered as a second choice.
Tagu, D; Martin, F
1995-01-01
Random sequencing of cDNA clones from Eucalyptus globulus-Pisolithus tinctorius ectomycorrhizal tissues was carried out to generate expressed sequence tags (ESTs). Database comparisons revealed that 42% of the cDNAs corresponded to previously sequenced genes. These ESTs represent efficient molecular markers to analyze changes in gene expression during the formation of the ectomycorrhizal symbiosis.
Directory of Open Access Journals (Sweden)
Wouter eOomens
2015-06-01
Full Text Available The concept of executive functions plays a prominent role in contemporary experimental and clinical studies on cognition. One paradigm used in this framework is the random number generation (RNG task, the execution of which demands aspects of executive functioning, specifically inhibition and working memory. Data from the RNG task are best seen as a series of successive events. However, traditional RNG measures that are used to quantify executive functioning are mostly summary statistics referring to deviations from mathematical randomness. In the current study, we explore the utility of recurrence quantification analysis (RQA, a nonlinear method that keeps the entire sequence intact, as a better way to describe executive functioning compared to traditional measures. To this aim, 242 first- and second-year students completed a non-paced RNG task. Principal component analysis of their data showed that traditional and RQA measures convey more or less the same information. However, RQA measures do so more parsimoniously and have a better interpretation.
Complexity and properties of a multidimensional Cat-Hadamard map for pseudo random number generation
Kim Hue, Ta Thi; Hoang, Thang Manh
2017-07-01
This paper presents a novel method to extend the Cat map from 2-dimension to higher dimension using the fast pseudo Hadamard Transform, and the resulted maps are called Cat-Hadamard maps. The complexity and properties of Cat-Hadamard maps are investigated under the point of view for cryptographic applications. In addition, we propose a method for constructing a pseudo random number generator using a novel design concept of the high dimensional Cat map. The simulation results show that the proposed generator fulfilled all the statistic tests of the NIST SP 800-90 A.
NullSeq: A Tool for Generating Random Coding Sequences with Desired Amino Acid and GC Contents.
Directory of Open Access Journals (Sweden)
Sophia S Liu
2016-11-01
Full Text Available The existence of over- and under-represented sequence motifs in genomes provides evidence of selective evolutionary pressures on biological mechanisms such as transcription, translation, ligand-substrate binding, and host immunity. In order to accurately identify motifs and other genome-scale patterns of interest, it is essential to be able to generate accurate null models that are appropriate for the sequences under study. While many tools have been developed to create random nucleotide sequences, protein coding sequences are subject to a unique set of constraints that complicates the process of generating appropriate null models. There are currently no tools available that allow users to create random coding sequences with specified amino acid composition and GC content for the purpose of hypothesis testing. Using the principle of maximum entropy, we developed a method that generates unbiased random sequences with pre-specified amino acid and GC content, which we have developed into a python package. Our method is the simplest way to obtain maximally unbiased random sequences that are subject to GC usage and primary amino acid sequence constraints. Furthermore, this approach can easily be expanded to create unbiased random sequences that incorporate more complicated constraints such as individual nucleotide usage or even di-nucleotide frequencies. The ability to generate correctly specified null models will allow researchers to accurately identify sequence motifs which will lead to a better understanding of biological processes as well as more effective engineering of biological systems.
Shah, Nameeta; Lankerovich, Michael; Lee, Hwahyung; Yoon, Jae-Geun; Schroeder, Brett; Foltz, Greg
2013-11-22
RNA-seq has spurred important gene fusion discoveries in a number of different cancers, including lung, prostate, breast, brain, thyroid and bladder carcinomas. Gene fusion discovery can potentially lead to the development of novel treatments that target the underlying genetic abnormalities. In this study, we provide comprehensive view of gene fusion landscape in 185 glioblastoma multiforme patients from two independent cohorts. Fusions occur in approximately 30-50% of GBM patient samples. In the Ivy Center cohort of 24 patients, 33% of samples harbored fusions that were validated by qPCR and Sanger sequencing. We were able to identify high-confidence gene fusions from RNA-seq data in 53% of the samples in a TCGA cohort of 161 patients. We identified 13 cases (8%) with fusions retaining a tyrosine kinase domain in the TCGA cohort and one case in the Ivy Center cohort. Ours is the first study to describe recurrent fusions involving non-coding genes. Genomic locations 7p11 and 12q14-15 harbor majority of the fusions. Fusions on 7p11 are formed in focally amplified EGFR locus whereas 12q14-15 fusions are formed by complex genomic rearrangements. All the fusions detected in this study can be further visualized and analyzed using our website: http://ivygap.swedish.org/fusions. Our study highlights the prevalence of gene fusions as one of the major genomic abnormalities in GBM. The majority of the fusions are private fusions, and a minority of these recur with low frequency. A small subset of patients with fusions of receptor tyrosine kinases can benefit from existing FDA approved drugs and drugs available in various clinical trials. Due to the low frequency and rarity of clinically relevant fusions, RNA-seq of GBM patient samples will be a vital tool for the identification of patient-specific fusions that can drive personalized therapy.
A Hardware Efficient Random Number Generator for Nonuniform Distributions with Arbitrary Precision
Directory of Open Access Journals (Sweden)
Christian de Schryver
2012-01-01
number generators is a very active research field. However, most state-of-the-art architectures are either tailored to specific distributions or use up a lot of hardware resources. At ReConFig 2010, we have presented a new design that saves up to 48% of area compared to state-of-the-art inversion-based implementation, usable for arbitrary distributions and precision. In this paper, we introduce a more flexible version together with a refined segmentation scheme that allows to further reduce the approximation error significantly. We provide a free software tool allowing users to implement their own distributions easily, and we have tested our random number generator thoroughly by statistic analysis and two application tests.
DEFF Research Database (Denmark)
Workman, Christopher; Krogh, Anders Stærmose
1999-01-01
This work investigates whether mRNA has a lower estimated folding free energy than random sequences. The free energy estimates are calculated by the mfold program for prediction of RNA secondary structures. For a set of 46 mRNAs it is shown that the predicted free energy is not significantly...... different from random sequences with the same dinucleotide distribution. For random sequences with the same mononucleotide distribution it has previously been shown that the native mRNA sequences have a lower predicted free energy, which indicates a more stable structure than random sequences. However......, dinucleotide content is important when assessing the significance of predicted free energy as the physical stability of RNA secondary structure is known to depend on dinucleotide base stacking energies. Even known RNA secondary structures, like tRNAs, can be shown to have predicted free energies...
On generalized difference sequence spaces of fuzzy numbers - doi: 10.4025/actascitechnol.v35i1.15566
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Binod Chandra Tripathy
2013-01-01
Full Text Available The idea of difference sequence space was introduced by Kizmaz (1981 and this concept was generalized by Tripathy and Esi (2006. In this article we introduced the paranormed sequence spaces cF(f,Λ,Δm,p, (f,Λ,Δm,p and (f,Λ,Δm,p of fuzzy numbers associated with the multiplier sequence Λ= (λk defined by a modulus function f. We study some of their properties like solidity, symmetricity, completeness etc. and prove some inclusion results.
Deke, John
2016-10-25
Cluster randomized controlled trials (CRCTs) often require a large number of clusters in order to detect small effects with high probability. However, there are contexts where it may be possible to design a CRCT with a much smaller number of clusters (10 or fewer) and still detect meaningful effects. The objective is to offer recommendations for best practices in design and analysis for small CRCTs. I use simulations to examine alternative design and analysis approaches. Specifically, I examine (1) which analytic approaches control Type I errors at the desired rate, (2) which design and analytic approaches yield the most power, (3) what is the design effect of spurious correlations, and (4) examples of specific scenarios under which impacts of different sizes can be detected with high probability. I find that (1) mixed effects modeling and using Ordinary Least Squares (OLS) on data aggregated to the cluster level both control the Type I error rate, (2) randomization within blocks is always recommended, but how best to account for blocking through covariate adjustment depends on whether the precision gains offset the degrees of freedom loss, (3) power calculations can be accurate when design effects from small sample, spurious correlations are taken into account, and (4) it is very difficult to detect small effects with just four clusters, but with six or more clusters, there are realistic circumstances under which small effects can be detected with high probability. © The Author(s) 2016.
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Dongfang Li
2015-10-01
Full Text Available Random number generators (RNG play an important role in many sensor network systems and applications, such as those requiring secure and robust communications. In this paper, we develop a high-security and high-throughput hardware true random number generator, called PUFKEY, which consists of two kinds of physical unclonable function (PUF elements. Combined with a conditioning algorithm, true random seeds are extracted from the noise on the start-up pattern of SRAM memories. These true random seeds contain full entropy. Then, the true random seeds are used as the input for a non-deterministic hardware RNG to generate a stream of true random bits with a throughput as high as 803 Mbps. The experimental results show that the bitstream generated by the proposed PUFKEY can pass all standard national institute of standards and technology (NIST randomness tests and is resilient to a wide range of security attacks.
Li, Dongfang; Lu, Zhaojun; Zou, Xuecheng; Liu, Zhenglin
2015-10-16
Random number generators (RNG) play an important role in many sensor network systems and applications, such as those requiring secure and robust communications. In this paper, we develop a high-security and high-throughput hardware true random number generator, called PUFKEY, which consists of two kinds of physical unclonable function (PUF) elements. Combined with a conditioning algorithm, true random seeds are extracted from the noise on the start-up pattern of SRAM memories. These true random seeds contain full entropy. Then, the true random seeds are used as the input for a non-deterministic hardware RNG to generate a stream of true random bits with a throughput as high as 803 Mbps. The experimental results show that the bitstream generated by the proposed PUFKEY can pass all standard national institute of standards and technology (NIST) randomness tests and is resilient to a wide range of security attacks.
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Jun Ding
2015-07-01
Full Text Available DNA sequencing identifies common and rare genetic variants for association studies, but studies typically focus on variants in nuclear DNA and ignore the mitochondrial genome. In fact, analyzing variants in mitochondrial DNA (mtDNA sequences presents special problems, which we resolve here with a general solution for the analysis of mtDNA in next-generation sequencing studies. The new program package comprises 1 an algorithm designed to identify mtDNA variants (i.e., homoplasmies and heteroplasmies, incorporating sequencing error rates at each base in a likelihood calculation and allowing allele fractions at a variant site to differ across individuals; and 2 an estimation of mtDNA copy number in a cell directly from whole-genome sequencing data. We also apply the methods to DNA sequence from lymphocytes of ~2,000 SardiNIA Project participants. As expected, mothers and offspring share all homoplasmies but a lesser proportion of heteroplasmies. Both homoplasmies and heteroplasmies show 5-fold higher transition/transversion ratios than variants in nuclear DNA. Also, heteroplasmy increases with age, though on average only ~1 heteroplasmy reaches the 4% level between ages 20 and 90. In addition, we find that mtDNA copy number averages ~110 copies/lymphocyte and is ~54% heritable, implying substantial genetic regulation of the level of mtDNA. Copy numbers also decrease modestly but significantly with age, and females on average have significantly more copies than males. The mtDNA copy numbers are significantly associated with waist circumference (p-value = 0.0031 and waist-hip ratio (p-value = 2.4×10-5, but not with body mass index, indicating an association with central fat distribution. To our knowledge, this is the largest population analysis to date of mtDNA dynamics, revealing the age-imposed increase in heteroplasmy, the relatively high heritability of copy number, and the association of copy number with metabolic traits.
A sequence-based method to predict the impact of regulatory variants using random forest.
Liu, Qiao; Gan, Mingxin; Jiang, Rui
2017-03-14
Most disease-associated variants identified by genome-wide association studies (GWAS) exist in noncoding regions. In spite of the common agreement that such variants may disrupt biological functions of their hosting regulatory elements, it remains a great challenge to characterize the risk of a genetic variant within the implicated genome sequence. Therefore, it is essential to develop an effective computational model that is not only capable of predicting the potential risk of a genetic variant but also valid in interpreting how the function of the genome is affected with the occurrence of the variant. We developed a method named kmerForest that used a random forest classifier with k-mer counts to predict accessible chromatin regions purely based on DNA sequences. We demonstrated that our method outperforms existing methods in distinguishing known accessible chromatin regions from random genomic sequences. Furthermore, the performance of our method can further be improved with the incorporation of sequence conservation features. Based on this model, we assessed importance of the k-mer features by a series of permutation experiments, and we characterized the risk of a single nucleotide polymorphism (SNP) on the function of the genome using the difference between the importance of the k-mer features affected by the occurrence of the SNP. We conducted a series of experiments and showed that our model can well discriminate between pathogenic and normal SNPs. Particularly, our model correctly prioritized SNPs that are proved to be enriched for the binding sites of FOXA1 in breast cancer cell lines from previous studies. We presented a novel method to interpret functional genetic variants purely base on DNA sequences. The proposed k-mer based score offers an effective means of measuring the impact of SNPs on the function of the genome, and thus shedding light on the identification of genetic risk factors underlying complex traits and diseases.
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Andreas Martin Lisewski
2008-09-01
Full Text Available The transmission of genomic information from coding sequence to protein structure during protein synthesis is subject to stochastic errors. To analyze transmission limits in the presence of spurious errors, Shannon's noisy channel theorem is applied to a communication channel between amino acid sequences and their structures established from a large-scale statistical analysis of protein atomic coordinates. While Shannon's theorem confirms that in close to native conformations information is transmitted with limited error probability, additional random errors in sequence (amino acid substitutions and in structure (structural defects trigger a decrease in communication capacity toward a Shannon limit at 0.010 bits per amino acid symbol at which communication breaks down. In several controls, simulated error rates above a critical threshold and models of unfolded structures always produce capacities below this limiting value. Thus an essential biological system can be realistically modeled as a digital communication channel that is (a sensitive to random errors and (b restricted by a Shannon error limit. This forms a novel basis for predictions consistent with observed rates of defective ribosomal products during protein synthesis, and with the estimated excess of mutual information in protein contact potentials.
Lisewski, Andreas Martin
2008-09-01
The transmission of genomic information from coding sequence to protein structure during protein synthesis is subject to stochastic errors. To analyze transmission limits in the presence of spurious errors, Shannon's noisy channel theorem is applied to a communication channel between amino acid sequences and their structures established from a large-scale statistical analysis of protein atomic coordinates. While Shannon's theorem confirms that in close to native conformations information is transmitted with limited error probability, additional random errors in sequence (amino acid substitutions) and in structure (structural defects) trigger a decrease in communication capacity toward a Shannon limit at 0.010 bits per amino acid symbol at which communication breaks down. In several controls, simulated error rates above a critical threshold and models of unfolded structures always produce capacities below this limiting value. Thus an essential biological system can be realistically modeled as a digital communication channel that is (a) sensitive to random errors and (b) restricted by a Shannon error limit. This forms a novel basis for predictions consistent with observed rates of defective ribosomal products during protein synthesis, and with the estimated excess of mutual information in protein contact potentials.
Chikayama, Eisuke; Kurotani, Atsushi; Kuroda, Yutaka; Yokoyama, Shigeyuki
2004-11-01
ProteoMix is a suite of JAVA programs for identifying, annotating and predicting regions of interest in large sets of amino acid sequences, according to systematic and consistent criteria. It is based on two concepts (1) the integration of results from different sequence analysis tools increases the prediction reliability; and (2) the integration protocol is critical and needs to be easily adaptable in a case-by-case manner. ProteoMix was designed to analyze simultaneously multiple protein sequences using several bioinformatics tools, merge the results of the analyses using logical functions and display them on an integrated viewer. In addition, new sequences can be added seamlessly to an analysis performed on an initial set of sequences. ProteoMix has a modular design, and bioinformatics tools are run on remote servers accessed using the Internet Simple Object Access Protocol (SOAP), ensuring the swift implementation of additional tools. ProteoMix has a user-friendly interactive graphical user interface environment and runs on PCs with Microsoft OS. ProteoMix is freely available for academic users at http://bio.gsc.riken.jp/ProteoMix/
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Yuki Kuniyoshi
Full Text Available Identification of immunoglobulin genes in hybridomas is essential for producing antibodies for research and clinical applications. A couple of methods such as RACE and degenerative PCR have been developed for determination of the Igh and Igl/Igk coding sequences (CDSs but it has been difficult to process a number of hybridomas both with accuracy and rapidness. Here, we propose a new strategy for antibody sequence determination by mRNA-seq of hybridomas. We demonstrated that hybridomas highly expressed the Igh and Igl/Igk genes and that de novo transcriptome assembly using mRNA-seq data enabled identification of the CDS of both Igh and Igl/Igk accurately. Furthermore, we estimated that only 30,000 sequenced reads are required to identify immunoglobulin sequences from four different hybridoma clones. Thus, our approach would facilitate determining variable CDSs drastically.
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Mindaugas Liogys
2011-08-01
Full Text Available Purpose—is to investigate a shift sequence-based approach efficiency then problem consisting of a high number of shifts. Research objectives:• Solve health care workers rostering problem using a shift sequence based method.• Measure its efficiency then number of shifts increases. Design/methodology/approach—Usually rostering problems are highly constrained.Constraints are classified to soft and hard constraints. Soft and hard constraints of the problem are additionally classified to: sequence constraints, schedule constraints and roster constraints. Sequence constraints are considered when constructing shift sequences. Schedule constraints are considered when constructing a schedule. Roster constraints are applied, then constructing overall solution, i.e. combining all schedules.Shift sequence based approach consists of two stages:• Shift sequences construction,• The construction of schedules.In the shift sequences construction stage, the shift sequences are constructed for each set of health care workers of different skill, considering sequence constraints. Shifts sequences are ranked by their penalties for easier retrieval in later stage.In schedules construction stage, schedules for each health care worker are constructed iteratively, using the shift sequences produced in stage 1. Shift sequence based method is an adaptive iterative method where health care workers who received the highest schedule penalties in the last iteration are scheduled first at the current iteration. During the roster construction, and after a schedule has been generated for the current health care worker, an improvement method based on an efficient greedy local search is carried out on the partial roster. It simply swaps any pair of shifts between two health care workers in the (partial roster, as long as the swaps satisfy hard constraints and decrease the roster penalty.Findings—Using shift sequence method for solving health care workers rostering
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Mindaugas Liogys
2013-08-01
Full Text Available Purpose—is to investigate a shift sequence-based approach efficiency then problem consisting of a high number of shifts.Research objectives:• Solve health care workers rostering problem using a shift sequence based method.• Measure its efficiency then number of shifts increases.Design/methodology/approach—Usually rostering problems are highly constrained. Constraints are classified to soft and hard constraints. Soft and hard constraints of the problem are additionally classified to: sequence constraints, schedule constraints and roster constraints. Sequence constraints are considered when constructing shift sequences. Schedule constraints are considered when constructing a schedule. Roster constraints are applied, then constructing overall solution, i.e. combining all schedules.Shift sequence based approach consists of two stages:• Shift sequences construction,• The construction of schedules.In the shift sequences construction stage, the shift sequences are constructed for each set of health care workers of different skill, considering sequence constraints. Shifts sequences are ranked by their penalties for easier retrieval in later stage.In schedules construction stage, schedules for each health care worker are constructed iteratively, using the shift sequences produced in stage 1.Shift sequence based method is an adaptive iterative method where health care workers who received the highest schedule penalties in the last iteration are scheduled first at the current iteration.During the roster construction, and after a schedule has been generated for the current health care worker, an improvement method based on an efficient greedy local search is carried out on the partial roster. It simply swaps any pair of shifts between two health care workers in the (partial roster, as long as the swaps satisfy hard constraints and decrease the roster penalty.Findings—Using shift sequence method for solving health care workers rostering problem
Koschate, J; Drescher, U; Thieschäfer, L; Heine, O; Baum, K; Hoffmann, U
2016-12-01
This study aims to compare cardiorespiratory kinetics as a response to a standardised work rate protocol with pseudo-random binary sequences between cycling and walking in young healthy subjects. Muscular and pulmonary oxygen uptake (V̇O2) kinetics as well as heart rate kinetics were expected to be similar for walking and cycling. Cardiac data and V̇O2 of 23 healthy young subjects were measured in response to pseudo-random binary sequences. Kinetics were assessed applying time series analysis. Higher maxima of cross-correlation functions between work rate and the respective parameter indicate faster kinetics responses. Muscular V̇O2 kinetics were estimated from heart rate and pulmonary V̇O2 using a circulatory model. Muscular (walking vs. cycling [mean±SD in arbitrary units]: 0.40±0.08 vs. 0.41±0.08) and pulmonary V̇O2 kinetics (0.35±0.06 vs. 0.35±0.06) were not different, although the time courses of the cross-correlation functions of pulmonary V̇O2 showed unexpected biphasic responses. Heart rate kinetics (0.50±0.14 vs. 0.40±0.14; P=0.017) was faster for walking. Regarding the biphasic cross-correlation functions of pulmonary V̇O2 during walking, the assessment of muscular V̇O2 kinetics via pseudo-random binary sequences requires a circulatory model to account for cardio-dynamic distortions. Faster heart rate kinetics for walking should be considered by comparing results from cycle and treadmill ergometry. © Georg Thieme Verlag KG Stuttgart · New York.
Tlelo-Cuautle, Esteban; de la Fraga, Luis Gerardo
2016-01-01
This book offers readers a clear guide to implementing engineering applications with FPGAs, from the mathematical description to the hardware synthesis, including discussion of VHDL programming and co-simulation issues. Coverage includes FPGA realizations such as: chaos generators that are described from their mathematical models; artificial neural networks (ANNs) to predict chaotic time series, for which a discussion of different ANN topologies is included, with different learning techniques and activation functions; random number generators (RNGs) that are realized using different chaos generators, and discussions of their maximum Lyapunov exponent values and entropies. Finally, optimized chaotic oscillators are synchronized and realized to implement a secure communication system that processes black and white and grey-scale images. In each application, readers will find VHDL programming guidelines and computer arithmetic issues, along with co-simulation examples with Active-HDL and Simulink. Readers will b...
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Zhang Xinmin
2011-05-01
Full Text Available Abstract Background In highly copy number variable (CNV regions such as the human defensin gene locus, comprehensive assessment of sequence variations is challenging. PCR approaches are practically restricted to tiny fractions, and next-generation sequencing (NGS approaches of whole individual genomes e.g. by the 1000 Genomes Project is confined by an affordable sequence depth. Combining target enrichment with NGS may represent a feasible approach. Results As a proof of principle, we enriched a ~850 kb section comprising the CNV defensin gene cluster DEFB, the invariable DEFA part and 11 control regions from two genomes by sequence capture and sequenced it by 454 technology. 6,651 differences to the human reference genome were found. Comparison to HapMap genotypes revealed sensitivities and specificities in the range of 94% to 99% for the identification of variations. Using error probabilities for rigorous filtering revealed 2,886 unique single nucleotide variations (SNVs including 358 putative novel ones. DEFB CN determinations by haplotype ratios were in agreement with alternative methods. Conclusion Although currently labor extensive and having high costs, target enriched NGS provides a powerful tool for the comprehensive assessment of SNVs in highly polymorphic CNV regions of individual genomes. Furthermore, it reveals considerable amounts of putative novel variations and simultaneously allows CN estimation.
Native Chromatin Immunoprecipitation-Sequencing (ChIP-Seq) from Low Cell Numbers.
Ribarska, Teodora; Gilfillan, Gregor D
2018-01-01
ChIP-seq is the current method of choice for genome-wide protein location analysis. Here, we present a native (non-cross-linked) ChIP procedure suitable for histone proteins, coupled with an efficient library preparation technique for subsequent next-generation sequencing. The method enables ChIP-seq starting with 50,000 or more cells.
White, S H
1994-04-01
This paper continues an examination of the hypothesis that modern proteins evolved from random heteropeptide sequences. In support of the hypothesis, White and Jacobs (1993, J Mol Evol 36:79-95) have shown that any sequence chosen randomly from a large collection of nonhomologous proteins has a 90% or better chance of having a lengthwise distribution of amino acids that is indistinguishable from the random expectation regardless of amino acid type. The goal of the present study was to investigate the possibility that the random-origin hypothesis could explain the lengths of modern protein sequences without invoking specific mechanisms such as gene duplication or exon splicing. The sets of sequences examined were taken from the 1989 PIR database and consisted of 1,792 "super-family" proteins selected to have little sequence identity, 623 E. coli sequences, and 398 human sequences. The length distributions of the proteins could be described with high significance by either of two closely related probability density functions: The gamma distribution with parameter 2 or the distribution for the sum of two exponential random independent variables. A simple theory for the distributions was developed which assumes that (1) protoprotein sequences had exponentially distributed random independent lengths, (2) the length dependence of protein stability determined which of these protoproteins could fold into compact primitive proteins and thereby attain the potential for biochemical activity, (3) the useful protein sequences were preserved by the primitive genome, and (4) the resulting distribution of sequence lengths is reflected by modern proteins. The theory successfully predicts the two observed distributions which can be distinguished by the functional form of the dependence of protein stability on length. The theory leads to three interesting conclusions. First, it predicts that a tetra-nucleotide was the signal for primitive translation termination. This prediction is
El Sharabasy, Sherif F; Soliman, Khaled A
2017-01-01
The date palm is an ancient domesticated plant with great diversity and has been cultivated in the Middle East and North Africa for at last 5000 years. Date palm cultivars are classified based on the fruit moisture content, as dry, semidry, and soft dates. There are a number of biochemical and molecular techniques available for characterization of the date palm variation. This chapter focuses on the DNA-based markers random amplified polymorphic DNA (RAPD) and inter-simple sequence repeats (ISSR) techniques, in addition to biochemical markers based on isozyme analysis. These techniques coupled with appropriate statistical tools proved useful for determining phylogenetic relationships among date palm cultivars and provide information resources for date palm gene banks.
Andrew J., Wood; R.Joel, Duff; Melvin J., Oliver; Department of Plant Biology, Southern Illinois University-Carbondale; Plant Stress and Water Conservation Unit, Cropping Systems Research Laboratory
1999-01-01
The desiccation-tolerant moss Tortula ruralis [Hedw.] Gaerten., Meyer & Scherb.has both a constitutive protection system and an active rehydration induced recovery mechanism apparently unique to bryophytes. Immediately following rehydration, desiccated T.ruralis gametophytes produce a set of polypeptides whose synthesis is unique to the rehydrated state. We report the construction of a cDNA expression library from the polysomal mRNA of desiccated gametophytes and the single-pass sequencing of...
Energy Technology Data Exchange (ETDEWEB)
Zietkiewicz, E.; Labuda, D. [Universite de Montreal, Que (Canada); Jurka, J. [Linus Pauling Institute, Palo Alto, CA (United States)
1994-09-01
Paleogenomics is the research activity aiming to reconstruct ancient genetic events and/or structures from the {open_quotes}fossil{close_quotes} genomic record. With about 120,000 copies, mammalian interspersed repeats, MIRs, represent the second most abundant family of short interspersed repeats in human DNA, only outnumbered by Alu elements. MIR consensus sequence of 100 nucleotides was reconstructed from 455 mutated copies preserved in contemporary genome (GenBank release 69). As no division into subfamilies was observed, we assume that this consensus represents an ancestral MIR sequence. To find out how far MIRs can be traced down the phylogenetic tree, we examined their distribution in a variety of mammalian and non-mammalian DNAs. Oligonucleotide primers based on the MIR consensus were used, one at a time, for PCR amplification of the genomic fragments flanked by MIR repeats (inter-MIR-PCR). Significant amplification in DNA samples from a variety of placental orders as well as marsupials and monotremes indicates that MIRs originated in early mammals. Sequence analysis is consistent with their proliferation during the Mesozoic era. Electrophoretic profiles of inter-MIR-PCR products are distinct among different species. Intra-species comparison of multiple human samples reveals polymorphic bands segregating as Mendelian traits which can be used as genetic markers in both mapping and fingerprinting.
A Comparison of mRNA Sequencing with Random Primed and 3'-Directed Libraries.
Xiong, Yuguang; Soumillon, Magali; Wu, Jie; Hansen, Jens; Hu, Bin; van Hasselt, Johan G C; Jayaraman, Gomathi; Lim, Ryan; Bouhaddou, Mehdi; Ornelas, Loren; Bochicchio, Jim; Lenaeus, Lindsay; Stocksdale, Jennifer; Shim, Jaehee; Gomez, Emilda; Sareen, Dhruv; Svendsen, Clive; Thompson, Leslie M; Mahajan, Milind; Iyengar, Ravi; Sobie, Eric A; Azeloglu, Evren U; Birtwistle, Marc R
2017-11-07
Creating a cDNA library for deep mRNA sequencing (mRNAseq) is generally done by random priming, creating multiple sequencing fragments along each transcript. A 3'-end-focused library approach cannot detect differential splicing, but has potentially higher throughput at a lower cost, along with the ability to improve quantification by using transcript molecule counting with unique molecular identifiers (UMI) that correct PCR bias. Here, we compare an implementation of such a 3'-digital gene expression (3'-DGE) approach with "conventional" random primed mRNAseq. Given our particular datasets on cultured human cardiomyocyte cell lines, we find that, while conventional mRNAseq detects ~15% more genes and needs ~500,000 fewer reads per sample for equivalent statistical power, the resulting differentially expressed genes, biological conclusions, and gene signatures are highly concordant between two techniques. We also find good quantitative agreement at the level of individual genes between two techniques for both read counts and fold changes between given conditions. We conclude that, for high-throughput applications, the potential cost savings associated with 3'-DGE approach are likely a reasonable tradeoff for modest reduction in sensitivity and inability to observe alternative splicing, and should enable many larger scale studies focusing on not only differential expression analysis, but also quantitative transcriptome profiling.
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M. Varchola
2009-12-01
Full Text Available This paper deals with an evaluation platform for cryptographic True Random Number Generators (TRNGs based on the hardware implementation of statistical tests for FPGAs. It was developed in order to provide an automatic tool that helps to speed up the TRNG design process and can provide new insights on the TRNG behavior as it will be shown on a particular example in the paper. It enables to test sufﬁcient statistical properties of various TRNG designs under various working conditions on the ﬂy. Moreover, the tests are suitable to be embedded into cryptographic hardware products in order to recognize TRNG output of weak quality and thus increase its robustness and reliability. Tests are fully compatible with the FIPS 140 standard and are implemented by the VHDL language as an IP-Core for vendor independent FPGAs. A recent Flash based Actel Fusion FPGA was chosen for preliminary experiments. The Actel version of the tests possesses an interface to the Actel’s CoreMP7 softcore processor that is fully compatible with the industry standard ARM7TDMI. Moreover, identical tests suite was implemented to the Xilinx Virtex 2 and 5 in order to compare the performance of the proposed solution with the performance of already published one based on the same FPGAs. It was achieved 25% and 65% greater clock frequency respectively while consuming almost equal resources of the Xilinx FPGAs. On the top of it, the proposed FIPS 140 architecture is capable of processing one random bit per one clock cycle which results in 311.5 Mbps throughput for Virtex 5 FPGA.
RSARF: Prediction of residue solvent accessibility from protein sequence using random forest method
Ganesan, Pugalenthi
2012-01-01
Prediction of protein structure from its amino acid sequence is still a challenging problem. The complete physicochemical understanding of protein folding is essential for the accurate structure prediction. Knowledge of residue solvent accessibility gives useful insights into protein structure prediction and function prediction. In this work, we propose a random forest method, RSARF, to predict residue accessible surface area from protein sequence information. The training and testing was performed using 120 proteins containing 22006 residues. For each residue, buried and exposed state was computed using five thresholds (0%, 5%, 10%, 25%, and 50%). The prediction accuracy for 0%, 5%, 10%, 25%, and 50% thresholds are 72.9%, 78.25%, 78.12%, 77.57% and 72.07% respectively. Further, comparison of RSARF with other methods using a benchmark dataset containing 20 proteins shows that our approach is useful for prediction of residue solvent accessibility from protein sequence without using structural information. The RSARF program, datasets and supplementary data are available at http://caps.ncbs.res.in/download/pugal/RSARF/. - See more at: http://www.eurekaselect.com/89216/article#sthash.pwVGFUjq.dpuf
Pawlowski, Marcin Piotr; Jara, Antonio; Ogorzalek, Maciej
2015-01-01
Entropy in computer security is associated with the unpredictability of a source of randomness. The random source with high entropy tends to achieve a uniform distribution of random values. Random number generators are one of the most important building blocks of cryptosystems. In constrained devices of the Internet of Things ecosystem, high entropy random number generators are hard to achieve due to hardware limitations. For the purpose of the random number generation in constrained devices, this work proposes a solution based on the least-significant bits concatenation entropy harvesting method. As a potential source of entropy, on-board integrated sensors (i.e., temperature, humidity and two different light sensors) have been analyzed. Additionally, the costs (i.e., time and memory consumption) of the presented approach have been measured. The results obtained from the proposed method with statistical fine tuning achieved a Shannon entropy of around 7.9 bits per byte of data for temperature and humidity sensors. The results showed that sensor-based random number generators are a valuable source of entropy with very small RAM and Flash memory requirements for constrained devices of the Internet of Things. PMID:26506357
Pawlowski, Marcin Piotr; Jara, Antonio; Ogorzalek, Maciej
2015-10-22
Entropy in computer security is associated with the unpredictability of a source of randomness. The random source with high entropy tends to achieve a uniform distribution of random values. Random number generators are one of the most important building blocks of cryptosystems. In constrained devices of the Internet of Things ecosystem, high entropy random number generators are hard to achieve due to hardware limitations. For the purpose of the random number generation in constrained devices, this work proposes a solution based on the least-significant bits concatenation entropy harvesting method. As a potential source of entropy, on-board integrated sensors (i.e., temperature, humidity and two different light sensors) have been analyzed. Additionally, the costs (i.e., time and memory consumption) of the presented approach have been measured. The results obtained from the proposed method with statistical fine tuning achieved a Shannon entropy of around 7.9 bits per byte of data for temperature and humidity sensors. The results showed that sensor-based random number generators are a valuable source of entropy with very small RAM and Flash memory requirements for constrained devices of the Internet of Things.
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Marcin Piotr Pawlowski
2015-10-01
Full Text Available Entropy in computer security is associated with the unpredictability of a source of randomness. The random source with high entropy tends to achieve a uniform distribution of random values. Random number generators are one of the most important building blocks of cryptosystems. In constrained devices of the Internet of Things ecosystem, high entropy random number generators are hard to achieve due to hardware limitations. For the purpose of the random number generation in constrained devices, this work proposes a solution based on the least-significant bits concatenation entropy harvesting method. As a potential source of entropy, on-board integrated sensors (i.e., temperature, humidity and two different light sensors have been analyzed. Additionally, the costs (i.e., time and memory consumption of the presented approach have been measured. The results obtained from the proposed method with statistical fine tuning achieved a Shannon entropy of around 7.9 bits per byte of data for temperature and humidity sensors. The results showed that sensor-based random number generators are a valuable source of entropy with very small RAM and Flash memory requirements for constrained devices of the Internet of Things.
Kim, Hyung-Yong; Choi, Jin-Woo; Lee, Jeong-Yeon; Kong, Gu
2017-04-18
Accurate detection of copy number alterations (CNAs) using next-generation sequencing technology is essential for the development and application of more precise medical treatments for human cancer. Here, we evaluated seven CNA estimation tools (ExomeCNV, CoNIFER, VarScan2, CODEX, ngCGH, saasCNV, and falcon) using whole-exome sequencing data from 419 breast cancer tumor-normal sample pairs from The Cancer Genome Atlas. Estimations generated using each tool were converted into gene-based copy numbers; concordance for gains and losses and the sensitivity and specificity of each tool were compared to validated copy numbers from a single nucleotide polymorphism reference array. The concordance and sensitivity of the tumor-normal pair methods for estimating CNAs (saasCNV, ExomeCNV, and VarScan2) were better than those of the tumor batch methods (CoNIFER and CODEX). SaasCNV had the highest gain and loss concordances (65.0%), sensitivity (69.4%), and specificity (89.1%) for estimating copy number gains or losses. These findings indicate that improved CNA detection algorithms are needed to more accurately interpret whole-exome sequencing results in human cancer.
Lundblad, Eirik W.; Xiao, Gaoping; Ko, Jae-hyeong; Altman, Sidney
2008-01-01
A method of inhibiting the expression of particular genes by using external guide sequences (EGSs) has been improved in its rapidity and specificity. Random EGSs that have 14-nt random sequences are used in the selection procedure for an EGS that attacks the mRNA for a gene in a particular location. A mixture of the random EGSs, the particular target RNA, and RNase P is used in the diagnostic procedure, which, after completion, is analyzed in a gel with suitable control lanes. Within a few ho...
Waszak, Sebastian M; Hasin, Yehudit; Zichner, Thomas; Olender, Tsviya; Keydar, Ifat; Khen, Miriam; Stütz, Adrian M; Schlattl, Andreas; Lancet, Doron; Korbel, Jan O
2010-11-11
Copy-number variations (CNVs) are widespread in the human genome, but comprehensive assignments of integer locus copy-numbers (i.e., copy-number genotypes) that, for example, enable discrimination of homozygous from heterozygous CNVs, have remained challenging. Here we present CopySeq, a novel computational approach with an underlying statistical framework that analyzes the depth-of-coverage of high-throughput DNA sequencing reads, and can incorporate paired-end and breakpoint junction analysis based CNV-analysis approaches, to infer locus copy-number genotypes. We benchmarked CopySeq by genotyping 500 chromosome 1 CNV regions in 150 personal genomes sequenced at low-coverage. The assessed copy-number genotypes were highly concordant with our performed qPCR experiments (Pearson correlation coefficient 0.94), and with the published results of two microarray platforms (95-99% concordance). We further demonstrated the utility of CopySeq for analyzing gene regions enriched for segmental duplications by comprehensively inferring copy-number genotypes in the CNV-enriched >800 olfactory receptor (OR) human gene and pseudogene loci. CopySeq revealed that OR loci display an extensive range of locus copy-numbers across individuals, with zero to two copies in some OR loci, and two to nine copies in others. Among genetic variants affecting OR loci we identified deleterious variants including CNVs and SNPs affecting ~15% and ~20% of the human OR gene repertoire, respectively, implying that genetic variants with a possible impact on smell perception are widespread. Finally, we found that for several OR loci the reference genome appears to represent a minor-frequency variant, implying a necessary revision of the OR repertoire for future functional studies. CopySeq can ascertain genomic structural variation in specific gene families as well as at a genome-wide scale, where it may enable the quantitative evaluation of CNVs in genome-wide association studies involving high
Qi, Qingwei; Lu, Sijia; Zhou, Xiya; Yao, Fengxia; Hao, Na; Yin, Guangjun; Li, Wenhui; Bai, Junjie; Li, Ning; Cram, David S
2016-06-01
The study aimed to determine whether cell-free fetal DNA (cffDNA) present in amniotic fluid supernatant can be used as a surrogate for amniocyte-based diagnosis of fetal chromosomal abnormalities. Amniocentesis was performed on 28 high-risk pregnancies. Amniocytes and the cffDNA fraction were prepared from the amniotic fluid samples. Chromosomal analysis of amniocytes was performed by either karyotyping or single nucleotide polymorphism (SNP) arrays. The corresponding cffDNA samples were blindly analyzed by copy number variation (CNV) sequencing in an independent laboratory. In the 28 matching amniocyte and cffDNA samples, there was a high diagnostic concordance for detection of euploidy, aneuploidy and CNVs. From ten samples referred for karyotyping, two aneuploidies (20%) were identified. From 18 samples referred for SNP array analysis, three pathogenic CNVs (16.7%) were identified. CNV sequencing of the 28 cffDNA samples also detected the two aneuploidies and the three pathogenic CNVs, giving an overall concordance rate of 100% for detection of pathogenic chromosome abnormalities. Compared with SNP array analysis, CNV sequencing returned a higher yield of benign or variants of unknown significance. Copy number variation sequencing of cffDNA represents an alternative approach to conventional prenatal diagnostic methods for reliable and accurate detection of clinically significant chromosomal abnormalities. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.
Aging effect on Executive Control in the Random Number Generation Test
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Amer Cavalheiro Hamdan
2006-12-01
Full Text Available The decline of abilities related to Executive Control –EC with aging has been related with the Pre-Frontal System neurobiological aging. This study compared the score obtained in the Random Number Generation Test (RNG by two groups: 30 college students (older than 18 and 36 elderly (older than 60. This last group was divided according to the criteria of schooling in up to 8 years of schooling and over 8 years of schooling. The results show that the younger participants scored 0,344 ± 0,04 in the RNG test; the elderly with up to 8 years of schooling punctuated 0,432 ± 0,10 and that those who studied for 9 years or more reached a mean of 0,393 ± 0,05. The statistical analysis of these data suggest that the elderly performance in the RNG test (0,420 ± 0,09 was significantly worse when compared to the performance of the younger participants (t (64 = -3,9927; p = 0,0001, which confirms that the manipulation and inhibitory control abilities of information are decreased in older people, probably due to the natural aging process of the Frontal Cortex. Keywords: neuropsychology; aging; executive functions.
Randomized controlled trial on timing and number of sampling for bile aspiration cytology.
Tsuchiya, Tomonori; Yokoyama, Yukihiro; Ebata, Tomoki; Igami, Tsuyoshi; Sugawara, Gen; Kato, Katsuyuki; Shimoyama, Yoshie; Nagino, Masato
2014-06-01
The issue on timing and number of bile sampling for exfoliative bile cytology is still unsettled. A total of 100 patients with cholangiocarcinoma undergoing resection after external biliary drainage were randomized into two groups: a 2-day group where bile was sampled five times per day for 2 days; and a 10-day group where bile was sampled once per day for 10 days (registered University Hospital Medical Information Network/ID 000005983). The outcome of 87 patients who underwent laparotomy was analyzed, 44 in the 2-day group and 43 in the 10-day group. There were no significant differences in patient characteristics between the two groups. Positivity after one sampling session was significantly lower in the 2-day group than in the 10-day group (17.0 ± 3.7% vs. 20.7 ± 3.5%, P = 0.034). However, cumulative positivity curves were similar and overlapped each other between both groups. The final cumulative positivity by the 10th sampling session was 52.3% in the 2-day group and 51.2% in the 10-day group. We observed a small increase in cumulative positivity after the 5th or 6th session in both groups. Bile cytology positivity is unlikely to be affected by sample time. © 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery.
Retterer, Kyle; Scuffins, Julie; Schmidt, Daniel; Lewis, Rachel; Pineda-Alvarez, Daniel; Stafford, Amanda; Schmidt, Lindsay; Warren, Stephanie; Gibellini, Federica; Kondakova, Anastasia; Blair, Amanda; Bale, Sherri; Matyakhina, Ludmila; Meck, Jeanne; Aradhya, Swaroop; Haverfield, Eden
2015-08-01
Detection of copy-number variation (CNV) is important for investigating many genetic disorders. Testing a large clinical cohort by array comparative genomic hybridization provides a deep perspective on the spectrum of pathogenic CNV. In this context, we describe a bioinformatics approach to extract CNV information from whole-exome sequencing and demonstrate its utility in clinical testing. Exon-focused arrays and whole-genome chromosomal microarray analysis were used to test 14,228 and 14,000 individuals, respectively. Based on these results, we developed an algorithm to detect deletions/duplications in whole-exome sequencing data and a novel whole-exome array. In the exon array cohort, we observed a positive detection rate of 2.4% (25 duplications, 318 deletions), of which 39% involved one or two exons. Chromosomal microarray analysis identified 3,345 CNVs affecting single genes (18%). We demonstrate that our whole-exome sequencing algorithm resolves CNVs of three or more exons. These results demonstrate the clinical utility of single-exon resolution in CNV assays. Our whole-exome sequencing algorithm approaches this resolution but is complemented by a whole-exome array to unambiguously identify intragenic CNVs and single-exon changes. These data illustrate the next advancements in CNV analysis through whole-exome sequencing and whole-exome array.Genet Med 17 8, 623-629.
The Hardy-Littlewood Problem for Regular and Uniformly Distributed Number Sequences
Oskolkov, V. A.
1995-04-01
Let H be the set of functions f(x) defined in (0,1), f(0+0)=f(1-0)=+\\infty, monotone in neighborhoods of singular points and such that the improper Riemann integral \\int_0^1 f(x)\\,dx converges. Let Q be an arbitrary set of sequences (\\{x_i\\})_{i=1}^\\infty uniformly distributed in the interval \\lbrack 0,1\\rbrack. We find the set of those pairs in H\\times Q for which the following equality is valid: \\displaystyle \\lim_{n\\to\\infty} \\frac{1}{n} \\sum_{i=1}^n f(\\{x_i\\})=\\int_0^1 f(x)\\,dx.
Some new sets of sequences of fuzzy numbers with respect to the partial metric.
Kadak, Uğur; Ozluk, Muharrem
2015-01-01
In this paper, we essentially deal with Köthe-Toeplitz duals of fuzzy level sets defined using a partial metric. Since the utilization of Zadeh's extension principle is quite difficult in practice, we prefer the idea of level sets in order to construct some classical notions. In this paper, we present the sets of bounded, convergent, and null series and the set of sequences of bounded variation of fuzzy level sets, based on the partial metric. We examine the relationships between these sets and their classical forms and give some properties including definitions, propositions, and various kinds of partial metric spaces of fuzzy level sets. Furthermore, we study some of their properties like completeness and duality. Finally, we obtain the Köthe-Toeplitz duals of fuzzy level sets with respect to the partial metric based on a partial ordering.
Ji, Haiting; Lu, Jingqiao; Wang, Jianjun; Li, Huawei; Lin, Xi
2014-01-01
Background Copy number variations (CNVs) are the major type of structural variation in the human genome, and are more common than DNA sequence variations in populations. CNVs are important factors for human genetic and phenotypic diversity. Many CNVs have been associated with either resistance to diseases or identified as the cause of diseases. Currently little is known about the role of CNVs in causing deafness. CNVs are currently not analyzed by conventional genetic analysis methods to stud...
The square root of 2 a dialogue concerning a number and a sequence
Flannery, David
2006-01-01
Using no more than the most basic algebra and geometry, Flannery (Cork Institute of Technology, Ireland) manages to convey not only why irrational numbers are fascinating, but how the whole enterprise of mathematical thinking is imaginative, intriguing, and engaging. A startlingly original and informative dialog, this book is a one-of-a-kind introduction to the pleasure and playful beauty of mathematical thinking.
Pseudo-random-bit-sequence phase modulation for reduced errors in a fiber optic gyroscope.
Chamoun, Jacob; Digonnet, Michel J F
2016-12-15
Low noise and drift in a laser-driven fiber optic gyroscope (FOG) are demonstrated by interrogating the sensor with a low-coherence laser. The laser coherence was reduced by broadening its optical spectrum using an external electro-optic phase modulator driven by either a sinusoidal or a pseudo-random bit sequence (PRBS) waveform. The noise reduction measured in a FOG driven by a modulated laser agrees with the calculations based on the broadened laser spectrum. Using PRBS modulation, the linewidth of a laser was broadened from 10 MHz to more than 10 GHz, leading to a measured FOG noise of only 0.00073 deg/√h and a drift of 0.023 deg/h. To the best of our knowledge, these are the lowest noise and drift reported in a laser-driven FOG, and this noise is below the requirement for the inertial navigation of aircraft.
Chen, Peng
2014-12-03
Background Protein-ligand binding is important for some proteins to perform their functions. Protein-ligand binding sites are the residues of proteins that physically bind to ligands. Despite of the recent advances in computational prediction for protein-ligand binding sites, the state-of-the-art methods search for similar, known structures of the query and predict the binding sites based on the solved structures. However, such structural information is not commonly available. Results In this paper, we propose a sequence-based approach to identify protein-ligand binding residues. We propose a combination technique to reduce the effects of different sliding residue windows in the process of encoding input feature vectors. Moreover, due to the highly imbalanced samples between the ligand-binding sites and non ligand-binding sites, we construct several balanced data sets, for each of which a random forest (RF)-based classifier is trained. The ensemble of these RF classifiers forms a sequence-based protein-ligand binding site predictor. Conclusions Experimental results on CASP9 and CASP8 data sets demonstrate that our method compares favorably with the state-of-the-art protein-ligand binding site prediction methods.
Paridaens, Tom; Van Wallendael, Glenn; De Neve, Wesley; Lambert, Peter
2017-09-25
The past decade has seen the introduction of new technologies that significantly lowered the cost of genome sequencing. As a result, the amount of genomic data that must be stored and transmitted is increasing exponentially. To mitigate storage and transmission issues, we introduce a framework for lossless compression of quality scores. This paper proposes AQUa, an adaptive framework for lossless compression of quality scores. To compress these quality scores, AQUa makes use of a configurable set of coding tools, extended with a Context-Adaptive Binary Arithmetic Coding scheme (CABAC). When benchmarking AQUa against generic single-pass compressors, file sizes are reduced by up to 38.49% when comparing with GNU Gzip and by up to 6.48% when comparing with 7-Zip at the Ultra Setting, while still providing support for random access. When comparing AQUa with the purpose-built, single-pass, and state-of-the-art compressor SCALCE, which does not support random access, file sizes are reduced by up to 21.14%. When comparing AQUa with the purpose-built, dual-pass, and state-of-the-art compressor QVZ, which does not support random access, file sizes are larger by 6.42% to 33.47%. However, for one test file, the file size is 0.38% smaller, illustrating the strength of our single-pass compression framework. This work has been spurred by the current activity on genomic information representation (MPEG-G) within the ISO/IEC SC29/WG11 technical committee. The software is available on Github: https://github.com/tparidae/AQUa. Tom Paridaens (tom.paridaens@ugent.be).
Directory of Open Access Journals (Sweden)
Hyun-Kyoung Kim
Full Text Available BACKGROUND: The concept of the utilization of rearranged ends for development of personalized biomarkers has attracted much attention owing to its clinical applicability. Although targeted next-generation sequencing (NGS for recurrent rearrangements has been successful in hematologic malignancies, its application to solid tumors is problematic due to the paucity of recurrent translocations. However, copy-number breakpoints (CNBs, which are abundant in solid tumors, can be utilized for identification of rearranged ends. METHOD: As a proof of concept, we performed targeted next-generation sequencing at copy-number breakpoints (TNGS-CNB in nine colon cancer cases including seven primary cancers and two cell lines, COLO205 and SW620. For deduction of CNBs, we developed a novel competitive single-nucleotide polymorphism (cSNP microarray method entailing CNB-region refinement by competitor DNA. RESULT: Using TNGS-CNB, 19 specific rearrangements out of 91 CNBs (20.9% were identified, and two polymerase chain reaction (PCR-amplifiable rearrangements were obtained in six cases (66.7%. And significantly, TNGS-CNB, with its high positive identification rate (82.6% of PCR-amplifiable rearrangements at candidate sites (19/23, just from filtering of aligned sequences, requires little effort for validation. CONCLUSION: Our results indicate that TNGS-CNB, with its utility for identification of rearrangements in solid tumors, can be successfully applied in the clinical laboratory for cancer-relapse and therapy-response monitoring.
Next-Generation Sequencing-Based Detection of Germline Copy Number Variations in BRCA1/BRCA2
DEFF Research Database (Denmark)
Schmidt, Ane Y; Hansen, Thomas V O; Ahlborn, Lise B
2017-01-01
identified by MLPA in 48 Danish breast and/or ovarian cancer families were analyzed. Moreover, 120 patient samples previously determined as negative for BRCA1/BRCA2 CNVs by MLPA were included in the analysis. Comparison of the NGS data with the data from MLPA revealed that the sensitivity was 100%, whereas......Genetic testing of BRCA1/2 includes screening for single nucleotide variants and small insertions/deletions and for larger copy number variations (CNVs), primarily by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). With the advent of next-generation sequencing (NGS...... the specificity was 95%. Taken together, this study validates a one-step bioinformatics work-flow to call germline BRCA1/2 CNVs using data obtained by NGS of a breast cancer gene panel. The work-flow represents a robust and easy-to-use method for full BRCA1/2 screening, which can be easily implemented in routine...
Lundblad, Eirik W; Xiao, Gaoping; Ko, Jae-Hyeong; Altman, Sidney
2008-02-19
A method of inhibiting the expression of particular genes by using external guide sequences (EGSs) has been improved in its rapidity and specificity. Random EGSs that have 14-nt random sequences are used in the selection procedure for an EGS that attacks the mRNA for a gene in a particular location. A mixture of the random EGSs, the particular target RNA, and RNase P is used in the diagnostic procedure, which, after completion, is analyzed in a gel with suitable control lanes. Within a few hours, the procedure is complete. The action of EGSs designed by an older method is compared with EGSs designed by the random EGS method on mRNAs from two bacterial pathogens.
Directory of Open Access Journals (Sweden)
Xuchao Li
Full Text Available BACKGROUND: Copy number variations (CNVs represent an important type of genetic variation that deeply impact phenotypic polymorphisms and human diseases. The advent of high-throughput sequencing technologies provides an opportunity to revolutionize the discovery of CNVs and to explore their relationship with diseases. However, most of the existing methods depend on sequencing depth and show instability with low sequence coverage. In this study, using low coverage whole-genome sequencing (LCS we have developed an effective population-scale CNV calling (PSCC method. METHODOLOGY/PRINCIPAL FINDINGS: In our novel method, two-step correction was used to remove biases caused by local GC content and complex genomic characteristics. We chose a binary segmentation method to locate CNV segments and designed combined statistics tests to ensure the stable performance of the false positive control. The simulation data showed that our PSCC method could achieve 99.7%/100% and 98.6%/100% sensitivity and specificity for over 300 kb CNV calling in the condition of LCS (∼2× and ultra LCS (∼0.2×, respectively. Finally, we applied this novel method to analyze 34 clinical samples with an average of 2× LCS. In the final results, all the 31 pathogenic CNVs identified by aCGH were successfully detected. In addition, the performance comparison revealed that our method had significant advantages over existing methods using ultra LCS. CONCLUSIONS/SIGNIFICANCE: Our study showed that PSCC can sensitively and reliably detect CNVs using low coverage or even ultra-low coverage data through population-scale sequencing.
Ji, Haiting; Lu, Jingqiao; Wang, Jianjun; Li, Huawei; Lin, Xi
2014-01-01
Copy number variations (CNVs) are the major type of structural variation in the human genome, and are more common than DNA sequence variations in populations. CNVs are important factors for human genetic and phenotypic diversity. Many CNVs have been associated with either resistance to diseases or identified as the cause of diseases. Currently little is known about the role of CNVs in causing deafness. CNVs are currently not analyzed by conventional genetic analysis methods to study deafness. Here we detected both DNA sequence variations and CNVs affecting 80 genes known to be required for normal hearing. Coding regions of the deafness genes were captured by a hybridization-based method and processed through the standard next-generation sequencing (NGS) protocol using the Illumina platform. Samples hybridized together in the same reaction were analyzed to obtain CNVs. A read depth based method was used to measure CNVs at the resolution of a single exon. Results were validated by the quantitative PCR (qPCR) based method. Among 79 sporadic cases clinically diagnosed with sensorineural hearing loss, we identified previously-reported disease-causing sequence mutations in 16 cases. In addition, we identified a total of 97 CNVs (72 CNV gains and 25 CNV losses) in 27 deafness genes. The CNVs included homozygous deletions which may directly give rise to deleterious effects on protein functions known to be essential for hearing, as well as heterozygous deletions and CNV gains compounded with sequence mutations in deafness genes that could potentially harm gene functions. We studied how CNVs in known deafness genes may result in deafness. Data provided here served as a basis to explain how CNVs disrupt normal functions of deafness genes. These results may significantly expand our understanding about how various types of genetic mutations cause deafness in humans.
Exact simulation of Brown-Resnick random fields at a finite number of locations
DEFF Research Database (Denmark)
Dieker, Ton; Mikosch, Thomas Valentin
2015-01-01
We propose an exact simulation method for Brown-Resnick random fields, building on new representations for these stationary max-stable fields. The main idea is to apply suitable changes of measure....
Directory of Open Access Journals (Sweden)
van Cuyck Hélène
2012-10-01
Full Text Available Abstract Background Streptococcus pneumoniae infections remain a major cause of morbidity and mortality worldwide. The diversity of pneumococci was first evidenced by serotyping of their capsular polysaccharides, responsible of virulence, resolving into more than 93 serotypes. Molecular tools have been developed to track the emergence and the spread of resistant, hyper virulent or non-vaccine type clones, particularly DNA-based methods using genetic polymorphism. Pulsed-Field Gel Electrophoresis analysis (PFGE and Multiple Loci Sequence Typing (MLST are the most frequently used genotyping techniques for S. pneumoniae. MLST is based on sequence comparison of housekeeping genes clustering isolates within sequence types. The availability of genome sequence data from different S. pneumoniae strains facilitated the search for other class of genetic markers as polymorphic DNA sequences for a Multiple-Locus Variable-Number Tandem-Repeat Analysis (MLVA. This study aims at confirming the relevance of MLVA of S. pneumoniae, comparing MLST and MLVA performances when discriminating subgroups of strains belonging to the same Sequence Type (ST, and defining a restricted but universal set of MLVA markers that has at least the same discriminatory power as MLST for S. pneumoniae by applying marker sets used by different authors on 331 isolates selected in UK. Results A minimum spanning tree was built including the serotypes distribution and comparing MLVA and MLST results. 220 MLVA types were determined grouped in 10 Sequence Types (ST. MLVA differentiated ST162 in two clonal complexes. A minimal set was defined: ms 25 and ms37, ms17, ms19, ms33, ms39, and ms40 including two universal markers. The selection was based on MLVA markers with a Diversity Index >0.8 and a selection of others depending of the population tested and the aim of the study. This set of 7 MLVA markers yields strain clusters similar to those obtained by MLST. Conclusions MLVA can discriminate
Li, Yuanwei; Ho, Chin Pang; Toulemonde, Matthieu; Chahal, Navtej; Senior, Roxy; Tang, Meng-Xing
2017-09-26
Myocardial contrast echocardiography (MCE) is an imaging technique that assesses left ventricle function and myocardial perfusion for the detection of coronary artery diseases. Automatic MCE perfusion quantification is challenging and requires accurate segmentation of the myocardium from noisy and time-varying images. Random forests (RF) have been successfully applied to many medical image segmentation tasks. However, the pixel-wise RF classifier ignores contextual relationships between label outputs of individual pixels. RF which only utilizes local appearance features is also susceptible to data suffering from large intensity variations. In this paper, we demonstrate how to overcome the above limitations of classic RF by presenting a fully automatic segmentation pipeline for myocardial segmentation in full-cycle 2D MCE data. Specifically, a statistical shape model is used to provide shape prior information that guide the RF segmentation in two ways. First, a novel shape model (SM) feature is incorporated into the RF framework to generate a more accurate RF probability map. Second, the shape model is fitted to the RF probability map to refine and constrain the final segmentation to plausible myocardial shapes. We further improve the performance by introducing a bounding box detection algorithm as a preprocessing step in the segmentation pipeline. Our approach on 2D image is further extended to 2D+t sequences which ensures temporal consistency in the final sequence segmentations. When evaluated on clinical MCE datasets, our proposed method achieves notable improvement in segmentation accuracy and outperforms other state-of-the-art methods including the classic RF and its variants, active shape model and image registration.
Reike, Dennis; Schwarz, Wolf
2016-01-01
The time required to determine the larger of 2 digits decreases with their numerical distance, and, for a given distance, increases with their magnitude (Moyer & Landauer, 1967). One detailed quantitative framework to account for these effects is provided by random walk models. These chronometric models describe how number-related noisy…
Directory of Open Access Journals (Sweden)
von Reumont Björn M
2010-03-01
Full Text Available Abstract Background Methods of alignment masking, which refers to the technique of excluding alignment blocks prior to tree reconstructions, have been successful in improving the signal-to-noise ratio in sequence alignments. However, the lack of formally well defined methods to identify randomness in sequence alignments has prevented a routine application of alignment masking. In this study, we compared the effects on tree reconstructions of the most commonly used profiling method (GBLOCKS which uses a predefined set of rules in combination with alignment masking, with a new profiling approach (ALISCORE based on Monte Carlo resampling within a sliding window, using different data sets and alignment methods. While the GBLOCKS approach excludes variable sections above a certain threshold which choice is left arbitrary, the ALISCORE algorithm is free of a priori rating of parameter space and therefore more objective. Results ALISCORE was successfully extended to amino acids using a proportional model and empirical substitution matrices to score randomness in multiple sequence alignments. A complex bootstrap resampling leads to an even distribution of scores of randomly similar sequences to assess randomness of the observed sequence similarity. Testing performance on real data, both masking methods, GBLOCKS and ALISCORE, helped to improve tree resolution. The sliding window approach was less sensitive to different alignments of identical data sets and performed equally well on all data sets. Concurrently, ALISCORE is capable of dealing with different substitution patterns and heterogeneous base composition. ALISCORE and the most relaxed GBLOCKS gap parameter setting performed best on all data sets. Correspondingly, Neighbor-Net analyses showed the most decrease in conflict. Conclusions Alignment masking improves signal-to-noise ratio in multiple sequence alignments prior to phylogenetic reconstruction. Given the robust performance of alignment
Gupta, Prabal; Singh, Balpreet; Arora, Krishan
2017-07-01
The very high peak to average power ratio (PAPR) is the biggest problem faced by OFDM system which ultimately causes distortion in the transmitted data. In the literatures various techniques have been proposed for the reduction of PAPR. One of the important technique which is known as Selected Mapping (SLM) or distortion-less technique proposed by several literature for the reduction of PAPR. But SLM technique generally uses several number of randomly designed phase sequence in frequency domain so that after inverse fast Fourier transform (IFFT) when data is converted into corresponding time domain sequence it can be optimized accordingly. Henceforth, in this paper we are proposing a higher number of novel phase sequence based SLM with 32-Quadrature amplitude modulation (QAM) under various sub carriers like 32, 64, 128, 256 and 512. Probabilistic analysis with the help of complementary cumulative distribution function (CCDF) clearly depicts the remarkable performance of our proposed algorithm in comparison with conventional OFDM system.
Least squares deconvolution for leak detection with a pseudo random binary sequence excitation
Nguyen, Si Tran Nguyen; Gong, Jinzhe; Lambert, Martin F.; Zecchin, Aaron C.; Simpson, Angus R.
2018-01-01
Leak detection and localisation is critical for water distribution system pipelines. This paper examines the use of the time-domain impulse response function (IRF) for leak detection and localisation in a pressurised water pipeline with a pseudo random binary sequence (PRBS) signal excitation. Compared to the conventional step wave generated using a single fast operation of a valve closure, a PRBS signal offers advantageous correlation properties, in that the signal has very low autocorrelation for lags different from zero and low cross correlation with other signals including noise and other interference. These properties result in a significant improvement in the IRF signal to noise ratio (SNR), leading to more accurate leak localisation. In this paper, the estimation of the system IRF is formulated as an optimisation problem in which the l2 norm of the IRF is minimised to suppress the impact of noise and interference sources. Both numerical and experimental data are used to verify the proposed technique. The resultant estimated IRF provides not only accurate leak location estimation, but also good sensitivity to small leak sizes due to the improved SNR.
Controlled random sequences: methods of convex analysis and problems with functional constraints
Piunovskii, A. B.
1998-12-01
ContentsIntroduction § 1. Controlled random sequences: main definitions and traditional approaches § 1.1. Description of the mathematical model § 1.2. Models with integral functionals § 1.3. Homogeneous Markov decision processes with average cost criteria § 2. Application of methods of convex analysis § 2.1. Properties of the space \\mathcal D § 2.2. Existence of optimal policies § 2.3. Sufficiency of selectors § 2.4. Preliminary results. The notion of an occupation measure § 2.5. Markov decision processes with total cost criteria and occupation measures § 2.6. Discounted costs and the corresponding occupation measures § 2.7. Average costs and ergodic occupation measures § 3. Problems with functional constraints § 3.1. General results § 3.2. Preliminary conclusions § 3.3. Markov decision processes with total cost criteria § 3.4. Homogeneous Markov decision processes with discounting § 3.5. Homogeneous Markov decision processes with average cost criteria § 3.6. Other constrained problems, related topics, and future prospectsConclusionAppendix. Elements of convex analysis and measure theory Bibliography
Lin, L.; Ng, C. S.; Bhattacharjee, A.
2008-11-01
We have recently obtained new scaling results in 2D for a ``tectonics model'' of coronal heating which suggest that the heating rate becomes independent of resistivity in a statistical steady state [Ng & Bhattacharjee, Astrophys. J., 675, 899 (2008)]. Here we extend our 2D results to 3D by means of numerical simulations. Random photospheric footpoint motion is applied for a time much longer than the correlation time to obtain converged average coronal heating rates. Simulations are done for different values of the Lundquist number to determine scaling. In the large Lundquist number limit, we recover the case in which the heating rate is independent of the Lundquist number, predicted by previous analysis as well as 2D simulations. In the same limit the average magnetic energy built up by the random footpoint motion saturates at a constant level, apparently limited by nonlinear processes, such as instabilities and/or magnetic reconnection.
Potiaumpai, Melanie; Martins, Maria Carolina Massoni; Wong, Claudia; Desai, Trusha; Rodriguez, Roberto; Mooney, Kiersten; Signorile, Joseph F
2017-02-01
To compare the difference in muscle activation between high-speed yoga and standard-speed yoga and to compare muscle activation of the transitions between poses and the held phases of a yoga pose. Randomized sequence crossover trial SETTING: A laboratory of neuromuscular research and active aging Interventions: Eight minutes of continuous Sun Salutation B was performed, at a high speed versus a standard-speed, separately. Electromyography was used to quantify normalized muscle activation patterns of eight upper and lower body muscles (pectoralis major, medial deltoids, lateral head of the triceps, middle fibers of the trapezius, vastus medialis, medial gastrocnemius, thoracic extensor spinae, and external obliques) during the high-speed and standard-speed yoga protocols. Difference in normalized muscle activation between high-speed yoga and standard-speed yoga. Normalized muscle activity signals were significantly higher in all eight muscles during the transition phases of poses compared to the held phases (pyoga across the entire session. Our results show that transitions from one held phase of a pose to another produces higher normalized muscle activity than the held phases of the poses and that overall activity is greater during highspeed yoga than standard-speed yoga. Therefore, the transition speed and associated number of poses should be considered when targeting specific improvements in performance. Copyright © 2016 Elsevier Ltd. All rights reserved.
Pseudorandom Number Generators for Mobile Devices: An Examination and Attempt to Improve Randomness
2013-09-01
what if the tickets are not properly mixed and instead are just put in a jar as they are being sold? What if the lottery tickets have different sizes...winner of the raffle randomly, and the lottery would not be considered fair. In the situation described in the previous paragraph, the raffle...official drawing the winning ticket is clearly a great risk to biasing the outcome. Therefore, mechanical raffle and lottery machines are widely used in
Energy Technology Data Exchange (ETDEWEB)
Kalchev, D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Ketelsen, C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Vassilevski, P. S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
2013-11-07
Our paper proposes an adaptive strategy for reusing a previously constructed coarse space by algebraic multigrid to construct a two-level solver for a problem with nearby characteristics. Furthermore, a main target application is the solution of the linear problems that appear throughout a sequence of Markov chain Monte Carlo simulations of subsurface flow with uncertain permeability field. We demonstrate the efficacy of the method with extensive set of numerical experiments.
Macken, C A; Perelson, A S
1986-01-01
Polymers containing small chemical groups (haptens) covalently attached at random along the chain are commonly used to initiate an immune response. Properties of the polymer such as its length, the spacing of the haptens, and the total number of haptens along the chain, correlate with its immune reactivity. Here we model the ability of many finite-sized cell surface receptors to bind simultaneously the haptens conjugated to a polymer chain. The binding sites on two different receptors or on separate parts of a multivalent receptor cannot be arbitrarily close to one another; so, in general, not all haptens along a polymer chain can be simultaneously bound by receptors. We develop an analogy between the steric hindrance among receptors detecting randomly placed haptens and the temporary locking of a Geiger counter that has detected a radioactive decay. Using renewal theory, we compute the probability distribution, and its moments, for the maximum number of haptens that can be simultaneously bound by monovalent receptors. We also model flexible bivalent receptors and obtain the mean and variance of the maximum number of receptors bound to randomly haptenated polymers, and the mean and variance of the maximum number of haptens bound. We demonstrate the importance of our results by applying them to immunological data and showing that, for polymers used in immunology, the effective valence of a polymer may be as much as 50% smaller than its nominal valence.
Orderings of weakly correlated random variables, and prime number races with many contestants
Harper, Adam; Lamzouri, Youness
2017-01-01
We investigate the race between prime numbers in many residue classes modulo $q$, assuming the standard conjectures GRH and LI. Among our results we exhibit, for the first time, prime races modulo $q$ with $n$ competitor classes where the biases do not dissolve when $n, q\\to \\infty$. We also study the leaders in the prime number race, obtaining asymptotic formulae for logarithmic densities when the number of competitors can be as large as a power of $q$, whereas previous methods could only al...
Gasparrini, S; Alborali, G L; Pitozzi, A; Guarneri, F; Giacomini, E; Baldo, V; Scali, F; Lazzaro, M; Boniotti, M B
2017-08-01
To evaluate and compare the capabilities of multilocus sequence typing (MLST) and multiple locus variable number tandem repeat analysis (MLVA) techniques to characterize Brachyspira hyodysenteriae isolates and to investigate the relationship between pleuromutilin resistance and genetic variability. MLST genotyping was performed on 180 B. hyodysenteriae isolates, and the results were evaluated considering profiles from 108 other strains previously reported in the database. In total, 37 sequence types were obtained. The MLVA approach completely characterized 172 strains and grouped the isolates into 22 different profiles. The combination of MLST and MLVA showed a slight increase in the discriminatory power, identifying 33 joint profiles. An antibiotic resistance analysis showed a reduction in the susceptibility to pleuromutilins over time, and a weak association between susceptibility to valnemulin and inclusion in clonal complex 4. MLST and MLVA are reliable methods for characterizing B. hyodysenteriae strains and they have comparable discriminatory power. The genotyping of B. hyodysenteriae isolates and a database of all the genetic profiles collected during the diagnostic activities could support traditional epidemiological investigations in identifying infection sources and routes of transmission among herds, and in developing more effective control measures. © 2017 The Society for Applied Microbiology.
Peng, Chien-Hua; Liao, Chun-Ta; Ng, Ka-Pou; Tai, An-Shun; Peng, Shih-Chi; Yeh, Jen-Pao; Chen, Shu-Jen; Tsao, Kuo-Chien; Yen, Tzu-Chen; Hsieh, Wen-Ping
2015-08-14
Ultra-deep targeted sequencing (UDT-Seq) has advanced our knowledge on the incidence and functional significance of somatic mutations. However, the utility of UDT-Seq in detecting copy number alterations (CNAs) remains unclear. With the goal of improving molecular prognostication and identifying new therapeutic targets, we designed this study to assess whether UDT-Seq may be useful for detecting CNA in oral cavity squamous cell carcinoma (OSCC). We sequenced a panel of clinically actionable cancer mutations in 310 formalin-fixed paraffin-embedded OSCC specimens. A linear model was developed to overcome uneven coverage across target regions and multiple samples. The 5-year rates of secondary primary tumors, local recurrence, neck recurrence, distant metastases, and survival served as the outcome measures. We confirmed the prognostic significance of the CNA signatures in an independent sample of 105 primary OSCC specimens. The CNA burden across 10 targeted genes was found to predict prognosis in two independent cohorts. FGFR1 and PIK3CAamplifications were associated with prognosis independent of clinical risk factors. Genes exhibiting CNA were clustered in the proteoglycan metabolism, the FOXO signaling, and the PI3K-AKT signaling pathways, for which targeted drugs are already available or currently under development. UDT-Seq is clinically useful to identify CNA, which significantly improve the prognostic information provided by traditional clinicopathological risk factors in OSCC patients.
Liu, Biao; Morrison, Carl D.; Johnson, Candace S.; Trump, Donald L.; Qin, Maochun; Conroy, Jeffrey C.; Wang, Jianmin; Liu, Song
2013-01-01
Accurate detection of somatic copy number variations (CNVs) is an essential part of cancer genome analysis, and plays an important role in oncotarget identifications. Next generation sequencing (NGS) holds the promise to revolutionize somatic CNV detection. In this review, we provide an overview of current analytic tools used for CNV detection in NGS-based cancer studies. We summarize the NGS data types used for CNV detection, decipher the principles for data preprocessing, segmentation, and interpretation, and discuss the challenges in somatic CNV detection. This review aims to provide a guide to the analytic tools used in NGS-based cancer CNV studies, and to discuss the important factors that researchers need to consider when analyzing NGS data for somatic CNV detections. PMID:24240121
Random number generator based on an integrated laser with on-chip optical feedback
Verschaffelt, Guy; Khoder, Mulham; Van der Sande, Guy
2017-11-01
We discuss the design and testing of a laser integrated with a long on-chip optical feedback section. The device and feedback section have been fabricated on a generic photonic integration platform using only standard building blocks. We have been able to integrate a 10 cm feedback length on a footprint of 5.5 mm2. By controlling the amount of feedback, we achieve chaotic dynamics in the long-cavity regime and show that the resulting dynamics is sufficiently complex in order to generate random bits based on the chaotic intensity fluctuation at a rate of 500 Mbits/s.
Application of random number generators in genetic algorithms to improve rainfall-runoff modelling
Czech Academy of Sciences Publication Activity Database
Chlumecký, M.; Buchtele, Josef; Richta, K.
2017-01-01
Roč. 553, October (2017), s. 350-355 ISSN 0022-1694 Institutional support: RVO:67985874 Keywords : genetic algorithm * optimisation * rainfall-runoff modeling * random generator Subject RIV: DA - Hydrology ; Limnology Impact factor: 3.483, year: 2016 https://ac.els-cdn.com/S0022169417305516/1-s2.0-S0022169417305516-main.pdf?_tid=fa1bad8a-bd6a-11e7-8567-00000aab0f27&acdnat=1509365462_a1335d3d997e9eab19e23b1eee977705
Directory of Open Access Journals (Sweden)
Seokhwi Kim
Full Text Available In the era of targeted therapy, mutation profiling of cancer is a crucial aspect of making therapeutic decisions. To characterize cancer at a molecular level, the use of formalin-fixed paraffin-embedded tissue is important. We tested the Ion AmpliSeq Cancer Hotspot Panel v2 and nCounter Copy Number Variation Assay in 89 formalin-fixed paraffin-embedded gastric cancer samples to determine whether they are applicable in archival clinical samples for personalized targeted therapies. We validated the results with Sanger sequencing, real-time quantitative PCR, fluorescence in situ hybridization and immunohistochemistry. Frequently detected somatic mutations included TP53 (28.17%, APC (10.1%, PIK3CA (5.6%, KRAS (4.5%, SMO (3.4%, STK11 (3.4%, CDKN2A (3.4% and SMAD4 (3.4%. Amplifications of HER2, CCNE1, MYC, KRAS and EGFR genes were observed in 8 (8.9%, 4 (4.5%, 2 (2.2%, 1 (1.1% and 1 (1.1% cases, respectively. In the cases with amplification, fluorescence in situ hybridization for HER2 verified gene amplification and immunohistochemistry for HER2, EGFR and CCNE1 verified the overexpression of proteins in tumor cells. In conclusion, we successfully performed semiconductor-based sequencing and nCounter copy number variation analyses in formalin-fixed paraffin-embedded gastric cancer samples. High-throughput screening in archival clinical samples enables faster, more accurate and cost-effective detection of hotspot mutations or amplification in genes.
Tomita, Toshihiro; Miyaji, Kousuke
2016-04-01
The dependence of random telegraph noise (RTN) amplitude distribution on the number of traps and trap depth position is investigated using three-dimensional Monte Carlo device simulation including random dopant fluctuation (RDF) in a 30 nm NAND multi level flash memory. The ΔV th tail distribution becomes broad at fixed double traps, indicating that the number of traps greatly affects the worst RTN characteristics. It is also found that for both fixed single and fixed double traps, the ΔV th distribution in the lowest cell threshold voltage (V th) state shows the broadest distribution among all cell V th states. This is because the drain current flows at the channel surface in the lowest cell V th state, while at a high cell V th, it flows at the deeper position owing to the fringing coupling between the control gate (CG) and the channel. In this work, the ΔV th distribution with the number of traps following the Poisson distribution is also considered to cope with the variations in trap number. As a result, it is found that the number of traps is an important factor for understanding RTN characteristics. In addition, considering trap position in the tunnel oxide thickness direction is also an important factor.
Ikehara, Kenji
2014-12-01
Only random processes should occur on the primitive Earth. In contrast, many ordered sequences are synthesized according to genetic information on the present Earth. In this communication, I have proposed an idea that protein 0th-order structures or specific amino acid compositions would mediate the transfer from random process to formation of ordered sequences, after formation of double-stranded genes.
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Kei-ichi Morita
Full Text Available Gorlin syndrome (GS is an autosomal dominant disorder that predisposes affected individuals to developmental defects and tumorigenesis, and caused mainly by heterozygous germline PTCH1 mutations. Despite exhaustive analysis, PTCH1 mutations are often unidentifiable in some patients; the failure to detect mutations is presumably because of mutations occurred in other causative genes or outside of analyzed regions of PTCH1, or copy number alterations (CNAs. In this study, we subjected a cohort of GS-affected individuals from six unrelated families to next-generation sequencing (NGS analysis for the combined screening of causative alterations in Hedgehog signaling pathway-related genes. Specific single nucleotide variations (SNVs of PTCH1 causing inferred amino acid changes were identified in four families (seven affected individuals, whereas CNAs within or around PTCH1 were found in two families in whom possible causative SNVs were not detected. Through a targeted resequencing of all coding exons, as well as simultaneous evaluation of copy number status using the alignment map files obtained via NGS, we found that GS phenotypes could be explained by PTCH1 mutations or deletions in all affected patients. Because it is advisable to evaluate CNAs of candidate causative genes in point mutation-negative cases, NGS methodology appears to be useful for improving molecular diagnosis through the simultaneous detection of both SNVs and CNAs in the targeted genes/regions.
Mersenne Twister: A 623-Dimensionally Equidistributed Uniform Pseudo-Random Number Generator
Matsumoto, Makoto; Nishimura, Takuji
1998-01-01
A new algorithm called Mersenne Twister (MT) is proposed for generating uniform pseudorandom numbers. For a particular choice of parameters, the algorithm provides a super astronomical period of 219937 - 1 and 623-dimensional equidistribution up to 32-bit accuracy, while using a working area of only 624 words. This is a new variant of the previously proposed generators, TGFSR, modified so as to admit a Mersenne-prime period. The characteristic polynomial has many terms. The distribution up to...
Quasi-Coherent Noise Jamming to LFM Radar Based on Pseudo-random Sequence Phase-modulation
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N. Tai
2015-12-01
Full Text Available A novel quasi-coherent noise jamming method is proposed against linear frequency modulation (LFM signal and pulse compression radar. Based on the structure of digital radio frequency memory (DRFM, the jamming signal is acquired by the pseudo-random sequence phase-modulation of sampled radar signal. The characteristic of jamming signal in time domain and frequency domain is analyzed in detail. Results of ambiguity function indicate that the blanket jamming effect along the range direction will be formed when jamming signal passes through the matched filter. By flexible controlling the parameters of interrupted-sampling pulse and pseudo-random sequence, different covering distances and jamming effects will be achieved. When the jamming power is equivalent, this jamming obtains higher process gain compared with non-coherent jamming. The jamming signal enhances the detection threshold and the real target avoids being detected. Simulation results and circuit engineering implementation validate that the jamming signal covers real target effectively.
Cryptographic pseudo-random sequences from the chaotic Hénon ...
Indian Academy of Sciences (India)
dimensional discrete-time Hénon map is proposed. Properties of the proposed sequences pertaining to linear complexity, linear complexity proﬁle, correlation and auto-correlation are investigated. All these properties of the sequences suggest a ...
Pan, Xiaoming; Wan, Baihui; Li, Chunchuan; Liu, Yu; Wang, Jing; Mou, Haijin; Liang, Xingguo
2014-08-20
Ligation-mediated polymerase chain reaction (LM-PCR) is a whole genome amplification (WGA) method, for which genomic DNA is cleaved into numerous fragments and then all of the fragments are amplified by PCR after attaching a universal end sequence. However, the self-ligation of these fragments could happen and may cause biased amplification and restriction of its application. To decrease the self-ligation probability, here we use type IIS restriction enzymes to digest genomic DNA into fragments with 4-5nt long overhangs with random sequences. After ligation to an adapter with random end sequences to above fragments, PCR is carried out and almost all present DNA sequences are amplified. In this study, whole genome of Vibrio parahaemolyticus was amplified and the amplification efficiency was evaluated by quantitative PCR. The results suggested that our approach could provide sufficient genomic DNA with good quality to meet requirements of various genetic analyses. Copyright © 2014. Published by Elsevier B.V.
Energy Technology Data Exchange (ETDEWEB)
Eason, R. O.
1980-09-01
Many data acquisition systems incorporate high-speed scanners to convert analog signals into digital format for further processing. Some systems multiplex many channels into a single scanner. A random access scanner whose scan sequence is specified by a table in random access memory will permit different scan rates on different channels. Generation of this scan table can be a tedious manual task when there are many channels (e.g. 50), when there are more than a few scan rates (e.g. 5), and/or when the ratio of the highest scan rate to the lowest scan rate becomes large (e.g. 100:1). An algorithm is developed which will generate these scan sequences for the random access scanner and implements the algorithm on a digital computer. Application of number theory to the mathematical statement of the problem led to development of several algorithms which were implemented in FORTRAN. The most efficient of these algorithms operates by partitioning the problem into a set of subproblems. Through recursion they solve each subproblem by partitioning it repeatedly into even smaller parts, continuing until a set of simple problems is created. From this process, a pictorial representation or wheel diagram of the problem can be constructed. From the wheel diagram and a description of the original problem, a scan table can be constructed. In addition, the wheel diagram can be used as a method of storing the scan sequence in a smaller amount of memory. The most efficient partitioning algorithm solved most scan table problems in less than a second of CPU time. Some types of problems, however, required as much as a few minutes of CPU time. 26 figures, 2 tables.
Palmeri, P.; Quinet, P.; Mendoza, C.; Bautista, M. A.; Witthoeft, M. C.; Kallman, T. R.
2016-01-01
Context. With the recent launching of the Hitomi X-ray space observatory, K lines and edges of chemical elements with low cosmic abundances, namely F, Na, P, Cl, K, Sc, Ti, V, Cr, Mn, Co, Cu and Zn, can be resolved and used to determine important properties of supernova remnants, galaxy clusters and accreting black holes and neutron stars.Aims. The second stage of the present ongoing project involves the computation of the accurate photoabsorption and photoionisation cross sections required to interpret the X-ray spectra of such trace elements.Methods. Depending on target complexity and computer tractability, ground-state cross sections are computed either with the close-coupling Breit-Pauli R-matrix method or with the autostructure atomic structure code in the isolated-resonance approximation. The intermediate-coupling scheme is used whenever possible. In order to determine a realistic K-edge behaviour for each species, both radiative and Auger dampings are taken into account, the latter being included in the R-matrix formalism by means of an optical potential.Results. Photoabsorption and total and partial photoionisation cross sections are reported for isoelectronic sequences with electron numbers 3 11 as they contribute significantly to the monotonic background of the cross section between the L and K edges. Configurations with 3d orbitals are important in rendering an accurate L edge, but they can be practically neglected in the K-edge region.
Lieber, Daniel S; Hershman, Steven G; Slate, Nancy G; Calvo, Sarah E; Sims, Katherine B; Schmahmann, Jeremy D; Mootha, Vamsi K
2014-03-06
D-bifunctional protein deficiency, caused by recessive mutations in HSD17B4, is a severe, infantile-onset disorder of peroxisomal fatty acid oxidation. Few affected patients survive past two years of age. Compound heterozygous mutations in HSD17B4 have also been reported in two sisters diagnosed with Perrault syndrome (MIM # 233400), who presented in adolescence with ovarian dysgenesis, hearing loss, and ataxia. An adult male presented with cerebellar ataxia, peripheral neuropathy, hearing loss, and azoospermia. The clinical presentation, in combination with biochemical findings in serum, urine, and muscle biopsy, suggested a mitochondrial disorder. Commercial genetic testing of 18 ataxia and mitochondrial disease genes was negative. Targeted exome sequencing followed by analysis of single nucleotide variants and small insertions/deletions failed to reveal a genetic basis of disease. Application of a computational algorithm to infer copy number variants (CNVs) from exome data revealed a heterozygous 12 kb deletion of exons 10-13 of HSD17B4 that was compounded with a rare missense variant (p.A196V) at a highly conserved residue. Retrospective review of patient records revealed mildly elevated ratios of pristanic:phytanic acid and arachidonic:docosahexaenoic acid, consistent with dysfunctional peroxisomal fatty acid oxidation. Our case expands the phenotypic spectrum of HSD17B4-deficiency, representing the first male case reported with infertility. Furthermore, it points to crosstalk between mitochondria and peroxisomes in HSD17B4-deficiency and Perrault syndrome.
Millau, Jean-François; Guillemette, Benoit; Gaudreau, Luc
2017-01-01
In this chapter we present a method allowing the screening of random sequences to discover essential aspects of unstructured protein regions in yeast. The approach can be applied to any protein with unstructured peptide sequences for which functions are difficult to decipher, for example the N-terminal tails of histones. The protocol first describes the building and preparation of a large library of random peptides in fusion with a protein of interest. Recent technical advances in oligonucleotide synthesis allow the construction of long random sequences up to 35 residues long. The protocol details the screening of the library in yeast for sequences that can functionally replace an unstructured domain in an essential protein in vivo. Our method typically identifies sequences that, while being totally different from the wild type, retain essential features allowing yeast to live. This collection of proteins with functional synthetic sequences can subsequently be used in phenotypic tests or genetic screens in order to discover genetic interaction.
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Clara Serra-Juhé
2017-05-01
Full Text Available Obesity is a multifactorial disorder with high heritability (50-75%, which is probably higher in early-onset and severe cases. Although rare monogenic forms and several genes and regions of susceptibility, including copy number variants (CNVs, have been described, the genetic causes underlying the disease still remain largely unknown. We searched for rare CNVs (>100kb in size, altering genes and present in 3 standard deviations above the mean at <3 years of age using SNP array molecular karyotypes. We then performed case control studies (480 EOO cases/480 non-obese controls with the validated CNVs and rare sequence variants (RSVs detected by targeted resequencing of selected CNV genes (n = 14, and also studied the inheritance patterns in available first-degree relatives. A higher burden of gain-type CNVs was detected in EOO cases versus controls (OR = 1.71, p-value = 0.0358. In addition to a gain of the NPY gene in a familial case with EOO and attention deficit hyperactivity disorder, likely pathogenic CNVs included gains of glutamate receptors (GRIK1, GRM7 and the X-linked gastrin-peptide receptor (GRPR, all inherited from obese parents. Putatively functional RSVs absent in controls were also identified in EOO cases at NPY, GRIK1 and GRPR. A patient with a heterozygous deletion disrupting two contiguous and related genes, SLCO4C1 and SLCO6A1, also had a missense RSV at SLCO4C1 on the other allele, suggestive of a recessive model. The genes identified showed a clear enrichment of shared co-expression partners with known genes strongly related to obesity, reinforcing their role in the pathophysiology of the disease. Our data reveal a higher burden of rare CNVs and RSVs in several related genes in patients with EOO compared to controls, and implicate NPY, GRPR, two glutamate receptors and SLCO4C1 in highly penetrant forms of familial obesity.
Serra-Juhé, Clara; Martos-Moreno, Gabriel Á; Bou de Pieri, Francesc; Flores, Raquel; González, Juan R; Rodríguez-Santiago, Benjamín; Argente, Jesús; Pérez-Jurado, Luis A
2017-05-01
Obesity is a multifactorial disorder with high heritability (50-75%), which is probably higher in early-onset and severe cases. Although rare monogenic forms and several genes and regions of susceptibility, including copy number variants (CNVs), have been described, the genetic causes underlying the disease still remain largely unknown. We searched for rare CNVs (>100kb in size, altering genes and present in obesity (EOO: body mass index >3 standard deviations above the mean at obese controls) with the validated CNVs and rare sequence variants (RSVs) detected by targeted resequencing of selected CNV genes (n = 14), and also studied the inheritance patterns in available first-degree relatives. A higher burden of gain-type CNVs was detected in EOO cases versus controls (OR = 1.71, p-value = 0.0358). In addition to a gain of the NPY gene in a familial case with EOO and attention deficit hyperactivity disorder, likely pathogenic CNVs included gains of glutamate receptors (GRIK1, GRM7) and the X-linked gastrin-peptide receptor (GRPR), all inherited from obese parents. Putatively functional RSVs absent in controls were also identified in EOO cases at NPY, GRIK1 and GRPR. A patient with a heterozygous deletion disrupting two contiguous and related genes, SLCO4C1 and SLCO6A1, also had a missense RSV at SLCO4C1 on the other allele, suggestive of a recessive model. The genes identified showed a clear enrichment of shared co-expression partners with known genes strongly related to obesity, reinforcing their role in the pathophysiology of the disease. Our data reveal a higher burden of rare CNVs and RSVs in several related genes in patients with EOO compared to controls, and implicate NPY, GRPR, two glutamate receptors and SLCO4C1 in highly penetrant forms of familial obesity.
KinMutRF: a random forest classifier of sequence variants in the human protein kinase superfamily
DEFF Research Database (Denmark)
Pons, Tirso; Vazquez, Miguel; Matey-Hernandez, María Luisa
2016-01-01
remains challenging: cells tolerate most genomic alterations and only a minor fraction disrupt molecular function sufficiently and drive disease. Results: KinMutRF is a novel random-forest method to automatically identify pathogenic variants in human kinases. Twenty six decision trees implemented......Background: The association between aberrant signal processing by protein kinases and human diseases such as cancer was established long time ago. However, understanding the link between sequence variants in the protein kinase superfamily and the mechanistic complex traits at the molecular level...... as a random forest ponder a battery of features that characterize the variants: a) at the gene level, including membership to a Kinbase group and Gene Ontology terms; b) at the PFAM domain level; and c) at the residue level, the types of amino acids involved, changes in biochemical properties, functional...
A specific brushing sequence and plaque removal efficacy : a randomized split-mouth design
van der Sluijs, E.; Slot, D.E.; Hennequin-Hoenderdos, N.L.; van der Weijden, G.A.
2018-01-01
Aim: It has been propagated by the dental care professionals to start toothbrushing the lingual aspect of teeth first. In general, it is assumed that these surfaces of teeth are more difficult to clean. The evidence to support this recommendation is sparse. Method: In this randomized controlled
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Regad Leslie
2010-01-01
Full Text Available Abstract Background In bioinformatics it is common to search for a pattern of interest in a potentially large set of rather short sequences (upstream gene regions, proteins, exons, etc.. Although many methodological approaches allow practitioners to compute the distribution of a pattern count in a random sequence generated by a Markov source, no specific developments have taken into account the counting of occurrences in a set of independent sequences. We aim to address this problem by deriving efficient approaches and algorithms to perform these computations both for low and high complexity patterns in the framework of homogeneous or heterogeneous Markov models. Results The latest advances in the field allowed us to use a technique of optimal Markov chain embedding based on deterministic finite automata to introduce three innovative algorithms. Algorithm 1 is the only one able to deal with heterogeneous models. It also permits to avoid any product of convolution of the pattern distribution in individual sequences. When working with homogeneous models, Algorithm 2 yields a dramatic reduction in the complexity by taking advantage of previous computations to obtain moment generating functions efficiently. In the particular case of low or moderate complexity patterns, Algorithm 3 exploits power computation and binary decomposition to further reduce the time complexity to a logarithmic scale. All these algorithms and their relative interest in comparison with existing ones were then tested and discussed on a toy-example and three biological data sets: structural patterns in protein loop structures, PROSITE signatures in a bacterial proteome, and transcription factors in upstream gene regions. On these data sets, we also compared our exact approaches to the tempting approximation that consists in concatenating the sequences in the data set into a single sequence. Conclusions Our algorithms prove to be effective and able to handle real data sets with
2010-01-01
Background In bioinformatics it is common to search for a pattern of interest in a potentially large set of rather short sequences (upstream gene regions, proteins, exons, etc.). Although many methodological approaches allow practitioners to compute the distribution of a pattern count in a random sequence generated by a Markov source, no specific developments have taken into account the counting of occurrences in a set of independent sequences. We aim to address this problem by deriving efficient approaches and algorithms to perform these computations both for low and high complexity patterns in the framework of homogeneous or heterogeneous Markov models. Results The latest advances in the field allowed us to use a technique of optimal Markov chain embedding based on deterministic finite automata to introduce three innovative algorithms. Algorithm 1 is the only one able to deal with heterogeneous models. It also permits to avoid any product of convolution of the pattern distribution in individual sequences. When working with homogeneous models, Algorithm 2 yields a dramatic reduction in the complexity by taking advantage of previous computations to obtain moment generating functions efficiently. In the particular case of low or moderate complexity patterns, Algorithm 3 exploits power computation and binary decomposition to further reduce the time complexity to a logarithmic scale. All these algorithms and their relative interest in comparison with existing ones were then tested and discussed on a toy-example and three biological data sets: structural patterns in protein loop structures, PROSITE signatures in a bacterial proteome, and transcription factors in upstream gene regions. On these data sets, we also compared our exact approaches to the tempting approximation that consists in concatenating the sequences in the data set into a single sequence. Conclusions Our algorithms prove to be effective and able to handle real data sets with multiple sequences, as well
Morse, Melvin L; Beem, Lance W
2011-12-01
Reiki therapy is documented for relief of pain and stress. Energetic healing has been documented to alter biologic markers of illness such as hematocrit. True random number generators are reported to be affected by energy healers and spiritually oriented conscious awareness. The patient was a then 54-year-old severely ill man who had hepatitis C types 1 and 2 and who did not improve with conventional therapy. He also suffered from obesity, the metabolic syndrome, asthma, and hypertension. He was treated with experimental high-dose interferon/riboviron therapy with resultant profound anemia and neutropenia. Energetic healing and Reiki therapy was administered initially to enhance the patient's sense of well-being and to relieve anxiety. Possible effects on the patient's absolute neutrophil count and hematocrit were incidentally noted. Reiki therapy was then initiated at times of profound neutropenia to assess its possible effect on the patient's absolute neutrophil count (ANC). Reiki and other energetic healing sessions were monitored with a true random number generator (RNG). Statistically significant relationships were documented between Reiki therapy, a quieting of the electronically created white noise of the RNG during healing sessions, and improvement in the patient's ANC. The immediate clinical result was that the patient could tolerate the high-dose interferon regimen without missing doses because of absolute neutropenia. The patient was initially a late responder to interferon and had been given a 5% chance of clearing the virus. He remains clear of the virus 1 year after treatment. The association between changes in the RNG, Reiki therapy, and a patient's ANC is the first to the authors' knowledge in the medical literature. Future studies assessing the effects of energetic healing on specific biologic markers of disease are anticipated. Concurrent use of a true RNG may prove to correlate with the effectiveness of energetic therapy.
Xian, Zhi-Hong; Cong, Wen-Ming; Zhang, Shu-Hui; Wu, Meng-Chao
2005-01-01
AIM: To study the genetic alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC), and to find the tumor related DNA fragments. METHODS: DNA isolated from tumors and corresponding noncancerous liver tissues of 56 HCC patients was amplified by random amplified polymorphic DNA (RAPD) with 10 random 10-mer arbitrary primers. The RAPD bands showing obvious differences in tumor tissue DNA corresponding to that of normal tissue were separated, purified, cloned and sequenced. DNA sequences were analyzed and compared with GenBank data. RESULTS: A total of 56 cases of HCC were demonstrated to have genetic alterations, which were detected by at least one primer. The detestability of genetic alterations ranged from 20% to 70% in each case, and 17.9% to 50% in each primer. Serum HBV infection, tumor size, histological grade, tumor capsule, as well as tumor intrahepatic metastasis, might be correlated with genetic alterations on certain primers. A band with a higher intensity of 480 bp or so amplified fragments in tumor DNA relative to normal DNA could be seen in 27 of 56 tumor samples using primer 4. Sequence analysis of these fragments showed 91% homology with Homo sapiens double homeobox protein DUX10 gene. CONCLUSION: Genetic alterations are a frequent event in HCC, and tumor related DNA fragments have been found in this study, which may be associated with hepatocarcin-ogenesis. RAPD is an effective method for the identification and analysis of genetic alterations in HCC, and may provide new information for further evaluating the molecular mechanism of hepatocarcinogenesis. PMID:15996039
Law of large numbers for the SIR model with random vertex weights on Erdős-Rényi graph
Xue, Xiaofeng
2017-11-01
In this paper we are concerned with the SIR model with random vertex weights on Erdős-Rényi graph G(n , p) . The Erdős-Rényi graph G(n , p) is generated from the complete graph Cn with n vertices through independently deleting each edge with probability (1 - p) . We assign i. i. d. copies of a positive r. v. ρ on each vertex as the vertex weights. For the SIR model, each vertex is in one of the three states 'susceptible', 'infective' and 'removed'. An infective vertex infects a given susceptible neighbor at rate proportional to the production of the weights of these two vertices. An infective vertex becomes removed at a constant rate. A removed vertex will never be infected again. We assume that at t = 0 there is no removed vertex and the number of infective vertices follows a Bernoulli distribution B(n , θ) . Our main result is a law of large numbers of the model. We give two deterministic functions HS(ψt) ,HV(ψt) for t ≥ 0 and show that for any t ≥ 0, HS(ψt) is the limit proportion of susceptible vertices and HV(ψt) is the limit of the mean capability of an infective vertex to infect a given susceptible neighbor at moment t as n grows to infinity.
Yamanaka, Syunsuke; Huh, Ji Young; Nishiyama, Kei; Hayashi, Hiroyuki
Long durational chest compression (CC) deteriorates cardiopulmonary resuscitation (CPR) quality. The appropriate number of CC personnel for minimizing rescuer's fatigue is mostly unknown. We determined the optimal number of personnel needed for 30-min CPR in a rescue-team. We conducted a randomized, manikin trial on healthcare providers. We divided them into Groups A to D according to the assigned different rest period to each group between the 2 min CCs. Groups A, B, C, and D performed CCs at 2, 4, 6, and 8 min rest period. All participants performed CCs for 30 min with a different rest period; participants allocated to Groups A, B, C, and D performed, eight, five, four, and three cycles, respectively. We compared a quality change of CCs among these groups to investigate how the assigned rest period affects the maintenance of CC quality during the 30-min CPR. This study involved 143 participants (male 58 [41%]; mean age, 24 years,) for the evaluation. As participants had less rest periods, the quality of their CCs such as sufficient depth ratio declined over 30-min CPR. A significant decrease in the sufficient CC depth ratio was observed in the second to the last cycle as compared to the first cycle. (median changes; A: -4%, B: -3%, C: 0%, and D: 0% p quality of CC during a 30-min CPR cycle. At least four personnel may be needed to reduce rescuer's fatigue for a 30-min CPR cycle when the team consists of men and women.
S. Zaccaria (Simone); M. El-Kebir (Mohammed); G.W. Klau (Gunnar); B.J. Raphael (Benjamin)
2017-01-01
textabstractCancer is an evolutionary process driven by somatic mutation. This process can be represented as a phylogenetic tree. Constructing such a phylogenetic tree from genome sequencing data is a challenging task due to the mutational complexity of cancer and the fact that nearly all cancer
Tang, X.; Wu, Z. M.; Wu, J. G.; Deng, T.; Fan, L.; Zhong, Z. Q.; Chen, J. J.; Xia, G. Q.
2015-01-01
We propose and experimentally demonstrate a novel technique to generate multi-channel high-speed physical random numbers (PRNs) by taking two chaotic signal outputs from mutually coupled semiconductor lasers (MC-SLs) as entropy sources. First, through controlling the operation parameters of the MC-SL system, two time-delay signature (TDS) suppressed chaotic signals can be obtained. Next, each of these two chaotic signals is sampled by an 8 bit analog-to-digital converter (ADC) with a sampling rate of 10 GHz, and then a bitwise exclusive-OR (XOR) operation on the corresponding bits in samples of the chaotic signal and its time delayed signal is implemented to obtain 8 bit XOR data. Furthermore, through selecting the five least significant bits (LSBs) of 8 bit XOR data to form 5 bit Boolean sequences, two sets of PRN streams with a rate up to 50 Gbits s-1 are generated and successfully pass the NIST statistical tests. Finally, merging these two sets of 50 Gbits s-1 PRN streams by an interleaving operation, another set of the 100 Gbits s-1 PRN stream, which meets all the quality criteria of NIST statistical tests, is also acquired.
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El mashad Noha
2009-01-01
Full Text Available Abstract Background Tuberculosis is a growing international health concern. It is the biggest killer among the infectious diseases in the world today. Early detection of drug resistance allows starting of an appropriate treatment. Resistance to drugs is due to particular genomic mutations in specific genes of Mycobacterium tuberculosis(MTB. The aim of this study was to identify the presence of Isoniazid (INH and Rifampicin(RIF drug resistance in new and previously treated tuberculosis (TB cases using DNA sequencing. Methods This study was carried out on 153 tuberculous patients with positive Bactec 460 culture for acid fast bacilli. Results Of the 153 patients, 105 (68.6% were new cases and 48 (31.4% were previously treated cases. Drug susceptibility testing on Bactec revealed 50 resistant cases for one or more of the first line antituberculous. Genotypic analysis was done only for rifampicin resistant specimens (23 cases and INH resistant specimens (26 cases to detect mutations responsible for drug resistance by PCR amplification of rpoB gene for rifampicin resistant cases and KatG gene for isoniazid resistant cases. Finally, DNA sequencing was done for detection of mutation within rpoB and KatG genes. Genotypic analysis of RIF resistant cases revealed that 20/23 cases (86.9% of RIF resistance were having rpoB gene mutation versus 3 cases (13.1% having no mutation with a high statistical significant difference between them (P Conclusion We can conclude that rifampicin resistance could be used as a useful surrogate marker for estimation of multidrug resistance. In addition, Genotypic method was superior to that of the traditional phenotypic method which is time-consuming taking several weeks or longer.
2013-01-01
month. Potentially eligible Māori were more likely than non-Māori to proceed to subsequent stages of recruitment. Differences between randomized Māori and non-Māori were evident (e.g. Maori were less likely to have established coronary artery disease). Conclusions Recruitment of equal numbers of indigenous and non-indigenous participants is possible if it is prioritised, adequately resourced and self-determination is supported. Trial registration The trial is registered with the Australian New Zealand Clinical Trial Registry ACTRN12606000067572 PMID:23800177
Folded Proteins Occur Frequently in Libraries of Random Amino Acid Sequences
Davidson, Alan R.; Sauer, Robert T.
1994-03-01
A library of synthetic genes encoding 80- to 100-residue proteins composed mainly of random combinations of glutamine (Q), leucine (L), and arginine (R) has been expressed in Escherichia coli. These genes also encode an epitope tag and six carboxyl-terminal histidines. Screening of this library by immunoblotting showed that 5% of these QLR proteins are expressed at readily detectable levels. Three well-expressed QLR proteins were purified and characterized. Each of these proteins has significant α-helical content, is largely resistant to degradation by Pronase, and has a distinct oligomeric structure. In addition, one protein unfolds in a highly cooperative manner. These properties of the QLR proteins demonstrate that they possess folded structures with some native-like properties. The QLR proteins differ from most natural proteins, however, in being remarkably resistant to denaturant-induced and thermal-induced unfolding and in being relatively insoluble in the absence of denaturants.
Fire detection system using random forest classification for image sequences of complex background
Kim, Onecue; Kang, Dong-Joong
2013-06-01
We present a fire alarm system based on image processing that detects fire accidents in various environments. To reduce false alarms that frequently appeared in earlier systems, we combined image features including color, motion, and blinking information. We specifically define the color conditions of fires in hue, saturation and value, and RGB color space. Fire features are represented as intensity variation, color mean and variance, motion, and image differences. Moreover, blinking fire features are modeled by using crossing patches. We propose an algorithm that classifies patches into fire or nonfire areas by using random forest supervised learning. We design an embedded surveillance device made with acrylonitrile butadiene styrene housing for stable fire detection in outdoor environments. The experimental results show that our algorithm works robustly in complex environments and is able to detect fires in real time.
The sequencing of adverbial clauses of time in academic English: Random forest modelling
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Abbas Ali Rezaee
2016-12-01
Full Text Available Adverbial clauses of time are positioned either before or after their associated main clauses. This study aims to assess the importance of discourse-pragmatics and processing-related constraints on the positioning of adverbial clauses of time in research articles of applied linguistics written by authors for whom English is considered a native language. Previous research has revealed that the ordering is co-determined by various factors from the domains of semantics and discourse-pragmatics (bridging, iconicity, and subordinator and language processing (deranking, length, and complexity. This research conducts a multifactorial analysis on the motivators of the positioning of adverbial clauses of time in 100 research articles of applied linguistics. The study will use a random forest of conditional inference trees as the statistical technique to measure the weights of the aforementioned variables. It was found that iconicity and bridging, which are factors associated with discourse and semantics, are the two most salient predictors of clause ordering.
a randomized controlled trial.
African Journals Online (AJOL)
milk, only an estimated one -fourth of neonates in India were breastfed within ... standard of care in India and mothers are informed about. 6 months of ... weeks postpartum. A random number sequence was generated using a com- puter program. Block randomization was used with a fixed block size of four. Concealment of ...
Carpena, Pedro; Bernaola-Galván, Pedro A; Carretero-Campos, Concepción; Coronado, Ana V
2016-11-01
Symbolic sequences have been extensively investigated in the past few years within the framework of statistical physics. Paradigmatic examples of such sequences are written texts, and deoxyribonucleic acid (DNA) and protein sequences. In these examples, the spatial distribution of a given symbol (a word, a DNA motif, an amino acid) is a key property usually related to the symbol importance in the sequence: The more uneven and far from random the symbol distribution, the higher the relevance of the symbol to the sequence. Thus, many techniques of analysis measure in some way the deviation of the symbol spatial distribution with respect to the random expectation. The problem is then to know the spatial distribution corresponding to randomness, which is typically considered to be either the geometric or the exponential distribution. However, these distributions are only valid for very large symbolic sequences and for many occurrences of the analyzed symbol. Here, we obtain analytically the exact, randomly expected spatial distribution valid for any sequence length and any symbol frequency, and we study its main properties. The knowledge of the distribution allows us to define a measure able to properly quantify the deviation from randomness of the symbol distribution, especially for short sequences and low symbol frequency. We apply the measure to the problem of keyword detection in written texts and to study amino acid clustering in protein sequences. In texts, we show how the results improve with respect to previous methods when short texts are analyzed. In proteins, which are typically short, we show how the measure quantifies unambiguously the amino acid clustering and characterize its spatial distribution.
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Yuichi eYamashita
2011-04-01
Full Text Available How the brain learns and generates temporal sequences is a fundamental issue in neuroscience. The production of birdsongs, a process which involves complex learned sequences, provides researchers with an excellent biological model for this topic. The Bengalese finch in particular learns a highly complex song with syntactical structure. The nucleus HVC (HVC, a premotor nucleus within the avian song system, plays a key role in generating the temporal structures of their songs. From lesion studies, the nucleus interfacialis (NIf projecting to the HVC is considered one of the essential regions that contribute to the complexity of their songs. However, the types of interaction between the HVC and the NIf that can produce complex syntactical songs remain unclear. In order to investigate the function of interactions between the HVC and NIf, we have proposed a neural network model based on previous biological evidence. The HVC is modeled by a recurrent neural network (RNN that learns to generate temporal patterns of songs. The NIf is modeled as a mechanism that provides auditory feedback to the HVC and generates random noise that feeds into the HVC. The model showed that complex syntactical songs can be replicated by simple interactions between deterministic dynamics of the RNN and random noise. In the current study, the plausibility of the model is tested by the comparison between the changes in the songs of actual birds induced by pharmacological inhibition of the NIf and the changes in the songs produced by the model resulting from modification of parameters representing NIf functions. The efficacy of the model demonstrates that the changes of songs induced by pharmacological inhibition of the NIf can be interpreted as a trade-off between the effects of noise and the effects of feedback on the dynamics of the RNN of the HVC. These facts suggest that the current model provides a convincing hypothesis for the functional role of NIf-HVC interaction.
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Xin Ma
2015-01-01
Full Text Available The prediction of RNA-binding proteins is one of the most challenging problems in computation biology. Although some studies have investigated this problem, the accuracy of prediction is still not sufficient. In this study, a highly accurate method was developed to predict RNA-binding proteins from amino acid sequences using random forests with the minimum redundancy maximum relevance (mRMR method, followed by incremental feature selection (IFS. We incorporated features of conjoint triad features and three novel features: binding propensity (BP, nonbinding propensity (NBP, and evolutionary information combined with physicochemical properties (EIPP. The results showed that these novel features have important roles in improving the performance of the predictor. Using the mRMR-IFS method, our predictor achieved the best performance (86.62% accuracy and 0.737 Matthews correlation coefficient. High prediction accuracy and successful prediction performance suggested that our method can be a useful approach to identify RNA-binding proteins from sequence information.
Jenke, Christian; Lindstedt, Björn Arne; Harmsen, Dag; Karch, Helge; Brandal, Lin Thorstensen; Mellmann, Alexander
2011-01-01
Multilocus variable-number tandem-repeat analysis (MLVA) was compared to multilocus sequence typing (MLST) to differentiate hemolytic uremic syndrome-associated enterohemorrhagic Escherichia coli strains. Although MLVA—like MLST—was highly discriminatory (index of diversity, 0.988 versus 0.984), a low level of concordance demonstrated the limited ability of MLVA to reflect long-term evolutionary events. PMID:21832012
Lockwood, M.; Owens, M. J.; Barnard, L.; Usoskin, I. G.
2016-11-01
We use sunspot-group observations from the Royal Greenwich Observatory (RGO) to investigate the effects of intercalibrating data from observers with different visual acuities. The tests are made by counting the number of groups [RB] above a variable cut-off threshold of observed total whole spot area (uncorrected for foreshortening) to simulate what a lower-acuity observer would have seen. The synthesised annual means of RB are then re-scaled to the full observed RGO group number [RA] using a variety of regression techniques. It is found that a very high correlation between RA and RB (r_{AB} > 0.98) does not prevent large errors in the intercalibration (for example sunspot-maximum values can be over 30 % too large even for such levels of r_{AB}). In generating the backbone sunspot number [R_{BB}], Svalgaard and Schatten ( Solar Phys., 2016) force regression fits to pass through the scatter-plot origin, which generates unreliable fits (the residuals do not form a normal distribution) and causes sunspot-cycle amplitudes to be exaggerated in the intercalibrated data. It is demonstrated that the use of Quantile-Quantile ("Q-Q") plots to test for a normal distribution is a useful indicator of erroneous and misleading regression fits. Ordinary least-squares linear fits, not forced to pass through the origin, are sometimes reliable (although the optimum method used is shown to be different when matching peak and average sunspot-group numbers). However, other fits are only reliable if non-linear regression is used. From these results it is entirely possible that the inflation of solar-cycle amplitudes in the backbone group sunspot number as one goes back in time, relative to related solar-terrestrial parameters, is entirely caused by the use of inappropriate and non-robust regression techniques to calibrate the sunspot data.
He, Xinjie; Tong, Shelley Xiuli
2017-08-10
The present study investigated the onset of statistical learning and examined whether the number of exposures to a repeated sequence influences the learning performance of children with dyslexia on a serial reaction time task. Three groups of children (29 with dyslexia, 29 age-matched controls, and 30 reading level-matched controls) were administered a serial reaction time task, and their statistical learning performances after a small and a large number of exposures (40 vs. 180 exposures) were recorded and compared. Children with dyslexia showed impaired statistical learning after a small number of exposures to a sequence, but intact statistical learning after a large number of exposures. In contrast, the age-matched and reading level-matched control groups showed intact statistical learning after both small and large numbers of exposures. Children with dyslexia also exhibited a slower learning rate than either control group. These results suggest that the amount of exposure to statistical patterns influences statistical learning performance in children with dyslexia.
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Christine eMohr
2015-01-01
Full Text Available Magical ideation and belief in the paranormal is considered to represent a trait-like character; people either believe in it or not. Yet, anecdotes indicate that exposure to an anomalous event can turn sceptics into believers. This transformation is likely to be accompanied by altered cognitive functioning such as impaired judgements of event likelihood. Here, we investigated whether the exposure to an anomalous event changes individuals’ explicit traditional (religious and non-traditional (e.g. paranormal beliefs as well as cognitive biases that have previously been associated with non-traditional beliefs, e.g. repetition avoidance when producing random numbers in a mental dice task. In a classroom, 91 students saw a magic demonstration after their psychology lecture. Before the demonstration, half of the students were told that the performance was done respectively by a conjuror (magician group or a psychic (psychic group. The instruction influenced participants’ explanations of the anomalous event. Participants in the magician, as compared to the psychic group, were more likely to explain the event through conjuring abilities while the reverse was true for psychic abilities. Moreover, these explanations correlated positively with their prior traditional and non-traditional beliefs. Finally, we observed that the psychic group showed more repetition avoidance than the magician group, and this effect remained the same regardless of whether assessed before or after the magic demonstration. We conclude that pre-existing beliefs and contextual suggestions both influence people’s interpretations of anomalous events and associated cognitive biases. Beliefs and associated cognitive biases are likely flexible well into adulthood and change with actual life events.
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Zhifu Sun
Full Text Available We used deep sequencing technology to profile the transcriptome, gene copy number, and CpG island methylation status simultaneously in eight commonly used breast cell lines to develop a model for how these genomic features are integrated in estrogen receptor positive (ER+ and negative breast cancer. Total mRNA sequence, gene copy number, and genomic CpG island methylation were carried out using the Illumina Genome Analyzer. Sequences were mapped to the human genome to obtain digitized gene expression data, DNA copy number in reference to the non-tumor cell line (MCF10A, and methylation status of 21,570 CpG islands to identify differentially expressed genes that were correlated with methylation or copy number changes. These were evaluated in a dataset from 129 primary breast tumors. Gene expression in cell lines was dominated by ER-associated genes. ER+ and ER- cell lines formed two distinct, stable clusters, and 1,873 genes were differentially expressed in the two groups. Part of chromosome 8 was deleted in all ER- cells and part of chromosome 17 amplified in all ER+ cells. These loci encoded 30 genes that were overexpressed in ER+ cells; 9 of these genes were overexpressed in ER+ tumors. We identified 149 differentially expressed genes that exhibited differential methylation of one or more CpG islands within 5 kb of the 5' end of the gene and for which mRNA abundance was inversely correlated with CpG island methylation status. In primary tumors we identified 84 genes that appear to be robust components of the methylation signature that we identified in ER+ cell lines. Our analyses reveal a global pattern of differential CpG island methylation that contributes to the transcriptome landscape of ER+ and ER- breast cancer cells and tumors. The role of gene amplification/deletion appears to more modest, although several potentially significant genes appear to be regulated by copy number aberrations.
Zhang, Zhongyang; Hao, Ke
2015-11-01
Cancer genomes exhibit profound somatic copy number alterations (SCNAs). Studying tumor SCNAs using massively parallel sequencing provides unprecedented resolution and meanwhile gives rise to new challenges in data analysis, complicated by tumor aneuploidy and heterogeneity as well as normal cell contamination. While the majority of read depth based methods utilize total sequencing depth alone for SCNA inference, the allele specific signals are undervalued. We proposed a joint segmentation and inference approach using both signals to meet some of the challenges. Our method consists of four major steps: 1) extracting read depth supporting reference and alternative alleles at each SNP/Indel locus and comparing the total read depth and alternative allele proportion between tumor and matched normal sample; 2) performing joint segmentation on the two signal dimensions; 3) correcting the copy number baseline from which the SCNA state is determined; 4) calling SCNA state for each segment based on both signal dimensions. The method is applicable to whole exome/genome sequencing (WES/WGS) as well as SNP array data in a tumor-control study. We applied the method to a dataset containing no SCNAs to test the specificity, created by pairing sequencing replicates of a single HapMap sample as normal/tumor pairs, as well as a large-scale WGS dataset consisting of 88 liver tumors along with adjacent normal tissues. Compared with representative methods, our method demonstrated improved accuracy, scalability to large cancer studies, capability in handling both sequencing and SNP array data, and the potential to improve the estimation of tumor ploidy and purity.
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Zhongyang Zhang
2015-11-01
Full Text Available Cancer genomes exhibit profound somatic copy number alterations (SCNAs. Studying tumor SCNAs using massively parallel sequencing provides unprecedented resolution and meanwhile gives rise to new challenges in data analysis, complicated by tumor aneuploidy and heterogeneity as well as normal cell contamination. While the majority of read depth based methods utilize total sequencing depth alone for SCNA inference, the allele specific signals are undervalued. We proposed a joint segmentation and inference approach using both signals to meet some of the challenges. Our method consists of four major steps: 1 extracting read depth supporting reference and alternative alleles at each SNP/Indel locus and comparing the total read depth and alternative allele proportion between tumor and matched normal sample; 2 performing joint segmentation on the two signal dimensions; 3 correcting the copy number baseline from which the SCNA state is determined; 4 calling SCNA state for each segment based on both signal dimensions. The method is applicable to whole exome/genome sequencing (WES/WGS as well as SNP array data in a tumor-control study. We applied the method to a dataset containing no SCNAs to test the specificity, created by pairing sequencing replicates of a single HapMap sample as normal/tumor pairs, as well as a large-scale WGS dataset consisting of 88 liver tumors along with adjacent normal tissues. Compared with representative methods, our method demonstrated improved accuracy, scalability to large cancer studies, capability in handling both sequencing and SNP array data, and the potential to improve the estimation of tumor ploidy and purity.
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Rosenstiel Philip
2010-04-01
Full Text Available Abstract Background The beta-defensin gene cluster (DEFB at chromosome 8p23.1 is one of the most copy number (CN variable regions of the human genome. Whereas individual DEFB CNs have been suggested as independent genetic risk factors for several diseases (e.g. psoriasis and Crohn's disease, the role of multisite sequence variations (MSV is less well understood and to date has only been reported for prostate cancer. Simultaneous assessment of MSVs and CNs can be achieved by PCR, cloning and Sanger sequencing, however, these methods are labour and cost intensive as well as prone to methodological bias introduced by bacterial cloning. Here, we demonstrate that amplicon sequencing of pooled individual PCR products by the 454 technology allows in-depth determination of MSV haplotypes and estimation of DEFB CNs in parallel. Results Six PCR products spread over ~87 kb of DEFB and harbouring 24 known MSVs were amplified from 11 DNA samples, pooled and sequenced on a Roche 454 GS FLX sequencer. From ~142,000 reads, ~120,000 haplotype calls (HC were inferred that identified 22 haplotypes ranging from 2 to 7 per amplicon. In addition to the 24 known MSVs, two additional sequence variations were detected. Minimal CNs were estimated from the ratio of HCs and compared to absolute CNs determined by alternative methods. Concordance in CNs was found for 7 samples, the CNs differed by one in 2 samples and the estimated minimal CN was half of the absolute in one sample. For 7 samples and 2 amplicons, the 454 haplotyping results were compared to those by cloning/Sanger sequencing. Intrinsic problems related to chimera formation during PCR and differences between haplotyping by 454 and cloning/Sanger sequencing are discussed. Conclusion Deep amplicon sequencing using the 454 technology yield thousands of HCs per amplicon for an affordable price and may represent an effective method for parallel haplotyping and CN estimation in small to medium-sized cohorts. The
Krishnan, Neeraja M.; Gaur, Prakhar; Chaudhary, Rakshit; Rao, Arjun A.; Panda, Binay
2012-01-01
Copy Number Alterations (CNAs) such as deletions and duplications; compose a larger percentage of genetic variations than single nucleotide polymorphisms or other structural variations in cancer genomes that undergo major chromosomal re-arrangements. It is, therefore, imperative to identify cancer-specific somatic copy number alterations (SCNAs), with respect to matched normal tissue, in order to understand their association with the disease. We have devised an accurate, sensitive, and easy-to-use tool, COPS, COpy number using Paired Samples, for detecting SCNAs. We rigorously tested the performance of COPS using short sequence simulated reads at various sizes and coverage of SCNAs, read depths, read lengths and also with real tumor:normal paired samples. We found COPS to perform better in comparison to other known SCNA detection tools for all evaluated parameters, namely, sensitivity (detection of true positives), specificity (detection of false positives) and size accuracy. COPS performed well for sequencing reads of all lengths when used with most upstream read alignment tools. Additionally, by incorporating a downstream boundary segmentation detection tool, the accuracy of SCNA boundaries was further improved. Here, we report an accurate, sensitive and easy to use tool in detecting cancer-specific SCNAs using short-read sequence data. In addition to cancer, COPS can be used for any disease as long as sequence reads from both disease and normal samples from the same individual are available. An added boundary segmentation detection module makes COPS detected SCNA boundaries more specific for the samples studied. COPS is available at ftp://115.119.160.213 with username “cops” and password “cops”. PMID:23110103
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Neeraja M Krishnan
Full Text Available Copy Number Alterations (CNAs such as deletions and duplications; compose a larger percentage of genetic variations than single nucleotide polymorphisms or other structural variations in cancer genomes that undergo major chromosomal re-arrangements. It is, therefore, imperative to identify cancer-specific somatic copy number alterations (SCNAs, with respect to matched normal tissue, in order to understand their association with the disease. We have devised an accurate, sensitive, and easy-to-use tool, COPS, COpy number using Paired Samples, for detecting SCNAs. We rigorously tested the performance of COPS using short sequence simulated reads at various sizes and coverage of SCNAs, read depths, read lengths and also with real tumor:normal paired samples. We found COPS to perform better in comparison to other known SCNA detection tools for all evaluated parameters, namely, sensitivity (detection of true positives, specificity (detection of false positives and size accuracy. COPS performed well for sequencing reads of all lengths when used with most upstream read alignment tools. Additionally, by incorporating a downstream boundary segmentation detection tool, the accuracy of SCNA boundaries was further improved. Here, we report an accurate, sensitive and easy to use tool in detecting cancer-specific SCNAs using short-read sequence data. In addition to cancer, COPS can be used for any disease as long as sequence reads from both disease and normal samples from the same individual are available. An added boundary segmentation detection module makes COPS detected SCNA boundaries more specific for the samples studied. COPS is available at ftp://115.119.160.213 with username "cops" and password "cops".
Energy Technology Data Exchange (ETDEWEB)
Pinnarò, Paola; Giordano, Carolina; Farneti, Alessia [Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome (Italy); Strigari, Lidia; Landoni, Valeria [Department of Physics, Regina Elena National Cancer Institute, Rome (Italy); Marucci, Laura; Petrongari, Maria Grazia [Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome (Italy); Sanguineti, Giuseppe, E-mail: sanguineti@ifo.it [Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome (Italy)
2016-07-15
Purpose: To compare long-term late local toxicity after either concomitant or sequential chemoradiation therapy after breast-conserving surgery. Methods and Materials: From 1997 to 2002, women aged 18 to 75 years who underwent breast-conserving surgery and axillary dissection for early breast cancer and in whom CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy was planned were randomized between concomitant and sequential radiation therapy. Radiation therapy was delivered to the whole breast through tangential fields to 50 Gy in 20 fractions over a period of 4 weeks, followed by an electron boost. Surviving patients were tentatively contacted and examined between March and September 2014. Patients in whom progressive disease had developed or who had undergone further breast surgery were excluded. Local toxicity (fibrosis, telangiectasia, and breast atrophy or retraction) was scored blindly to the treatment received. A logistic regression was run to investigate the effect of treatment sequence after correction for several patient-, treatment-, and tumor-related covariates on selected endpoints. The median time to cross-sectional analysis was 15.7 years (range, 12.0-17.8 years). Results: Of 206 patients randomized, 154 (74.8%) were potentially eligible. Of these, 43 (27.9%) refused participation and 4 (2.6%) had been lost to follow-up, and for 5 (3.2%), we could not restore planning data; thus, the final number of analyzed patients was 102. No grade 4 toxicity had been observed, whereas the number of grade 3 toxicity events was low (<8%) for each item, allowing pooling of grade 2 and 3 events for further analysis. Treatment sequence (concomitant vs sequential) was an independent predictor of grade 2 or 3 fibrosis according to both the National Cancer Institute Common Terminology Criteria for Adverse Events (odds ratio [OR], 4.05; 95% confidence interval [CI], 1.34-12.2; P=.013) and the SOMA (Subjective, Objective, Management and Analytic
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Calvayrac, Florent [Laboratoire de Physique de l' Etat Condense, UMR CNRS 6087 and FR 2575, Universite du Maine, 72085 Le Mans Cedex 9 (France)
2005-09-01
We present known and new applications of pseudo random numbers and of the Metropolis algorithm to phenomena of physical and mechanical interest, such as the search of simple clusters isomers with interactive visualization, or vehicle motion planning. The progression towards complicated problems was used with first-year graduate students who wrote most of the programs presented here. We argue that the use of pseudo random numbers in simulation and extrema research programs in teaching numerical methods in physics allows one to get quick programs and physically meaningful and demonstrative results without recurring to the advanced numerical analysis methods.
Information Theory of DNA Sequencing
Motahari, Abolfazl; Tse, David
2012-01-01
DNA sequencing is the basic workhorse of modern day biology and medicine. Shotgun sequencing is the dominant technique used: many randomly located short fragments called reads are extracted from the DNA sequence, and these reads are assembled to reconstruct the original sequence. By drawing an analogy between the DNA sequencing problem and the classic communication problem, we define an information theoretic notion of sequencing capacity. This is the maximum number of DNA base pairs that can be resolved reliably per read, and provides a fundamental limit to the performance that can be achieved by any assembly algorithm. We compute the sequencing capacity explicitly for a simple statistical model of the DNA sequence and the read process. Using this framework, we also study the impact of noise in the read process on the sequencing capacity.
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Andrew P. Morgan
2016-12-01
Full Text Available Wild-derived mouse inbred strains are becoming increasingly popular for complex traits analysis, evolutionary studies, and systems genetics. Here, we report the whole-genome sequencing of two wild-derived mouse inbred strains, LEWES/EiJ and ZALENDE/EiJ, of Mus musculus domesticus origin. These two inbred strains were selected based on their geographic origin, karyotype, and use in ongoing research. We generated 14× and 18× coverage sequence, respectively, and discovered over 1.1 million novel variants, most of which are private to one of these strains. This report expands the number of wild-derived inbred genomes in the Mus genus from six to eight. The sequence variation can be accessed via an online query tool; variant calls (VCF format and alignments (BAM format are available for download from a dedicated ftp site. Finally, the sequencing data have also been stored in a lossless, compressed, and indexed format using the multi-string Burrows-Wheeler transform. All data can be used without restriction.
Morgan, Andrew P; Didion, John P; Doran, Anthony G; Holt, James M; McMillan, Leonard; Keane, Thomas M; de Villena, Fernando Pardo-Manuel
2016-12-07
Wild-derived mouse inbred strains are becoming increasingly popular for complex traits analysis, evolutionary studies, and systems genetics. Here, we report the whole-genome sequencing of two wild-derived mouse inbred strains, LEWES/EiJ and ZALENDE/EiJ, of Mus musculus domesticus origin. These two inbred strains were selected based on their geographic origin, karyotype, and use in ongoing research. We generated 14× and 18× coverage sequence, respectively, and discovered over 1.1 million novel variants, most of which are private to one of these strains. This report expands the number of wild-derived inbred genomes in the Mus genus from six to eight. The sequence variation can be accessed via an online query tool; variant calls (VCF format) and alignments (BAM format) are available for download from a dedicated ftp site. Finally, the sequencing data have also been stored in a lossless, compressed, and indexed format using the multi-string Burrows-Wheeler transform. All data can be used without restriction. Copyright © 2016 Morgan et al.
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Zou Fei
2010-10-01
Full Text Available Abstract Background The primer and amplicon length have been found to affect PCR based estimates of microbial diversity by pyrosequencing, while other PCR conditions have not been addressed using any deep sequencing method. The present study determined the effects of polymerase, template dilution and PCR cycle number using the Solexa platform. Results The PfuUltra II Fusion HS DNA Polymerase (Stratagene with higher fidelity showed lower amount of PCR artifacts and determined lower taxa richness than the Ex Taq (Takara. More importantly, the two polymerases showed different efficiencies for amplifying some of very abundant sequences, and determined significantly different community structures. As expected, the dilution of the DNA template resulted in a reduced estimation of taxa richness, particularly at the 200 fold dilution level, but the community structures were similar for all dilution levels. The 30 cycle group increased the PCR artifacts while comparing to the 25 cycle group, but the determined taxa richness was lower than that of the 25 cycle group. The PCR cycle number did not changed the microbial community structure significantly. Conclusions These results highlight the PCR conditions, particularly the polymerase, have significant effect on the analysis of microbial diversity with next generation sequencing methods.
Yu, Zhenhua; Liu, Yuanning; Shen, Yi; Wang, Minghui; Li, Ao
2014-09-15
Whole-genome sequencing of tumor samples has been demonstrated as an efficient approach for comprehensive analysis of genomic aberrations in cancer genome. Critical issues such as tumor impurity and aneuploidy, GC-content and mappability bias have been reported to complicate identification of copy number alteration and loss of heterozygosity in complex tumor samples. Therefore, efficient computational methods are required to address these issues. We introduce CLImAT (CNA and LOH Assessment in Impure and Aneuploid Tumors), a bioinformatics tool for identification of genomic aberrations from tumor samples using whole-genome sequencing data. Without requiring a matched normal sample, CLImAT takes integrated analysis of read depth and allelic frequency and provides extensive data processing procedures including GC-content and mappability correction of read depth and quantile normalization of B-allele frequency. CLImAT accurately identifies copy number alteration and loss of heterozygosity even for highly impure tumor samples with aneuploidy. We evaluate CLImAT on both simulated and real DNA sequencing data to demonstrate its ability to infer tumor impurity and ploidy and identify genomic aberrations in complex tumor samples. The CLImAT software package can be freely downloaded at http://bioinformatics.ustc.edu.cn/CLImAT/. © The Author 2014. Published by Oxford University Press.
AlSagob, Maysoon; Colak, Dilek; Kaya, Namik
2015-05-01
Autism spectrum disorder (ASD) is a large group of neurodevelopmental conditions that share common characteristics such as social and language impairment and repetitive and stereotypic behaviors. It is reported that ASD is on increase in recent years reaching ratios up to 1 in 68 children. The disease is seen four times more frequently in males than females. ASD is heritable with complex inheritance and genetic heterogeneity, and frequently coexists with other diseases such as intellectual disability, seizure disorders, and fragile-x. Recent advances in genomic technologies have led to a greater understanding of genetic mechanisms in ASD, discovery of novel genetic loci and risk factors, as well as submicroscopic chromosomal changes also known as copy number variations (CNVs). Here we review recent developments in the genetics field and hereditary and sporadic CNVs leading to ASD.
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Meena Shah
Full Text Available It is unclear how high-protein (HP and high-monounsaturated fat (HMF meals affect postprandial blood lipids and lipoprotein particle numbers (LPN.To compare a HP versus a HMF meal on postprandial lipid and LPN responses.Twenty-four participants (age: 36.3±15.0 years; body mass index: 23.6±2.0 kg/m2; 45.8% female were fed a HP (31.9% energy from protein and a HMF (35.2% fat and 20.7% monounsaturated fat meal in a randomized cross-over trial design. Energy and carbohydrate content were the same across meals. Blood samples were drawn in the fasting state and 3 hour postprandial state, and assessed for lipids and LPN.Repeated measures analysis showed a significant (p<0.05 treatment by time interaction effect for triglycerides (TG, the primary variable, total high-density lipoprotein particles (T-HDLP and T-HDLP minus large-buoyant high-density lipoprotein 2b (T-HDLP-LB-HDL2b. HP versus HMF condition led to significantly lower TG at 120 (geometric mean: 90.1 (95% confidence interval (CI: 76.4-106.3 vs. 146.5 (124.2-172.9 mg/dL and 180 (101.4 (83.1-123.8 vs. 148.7 (121.9-181.4 mg/dL min and higher T-HDLP at 120 (mean difference: 297.3 (95% CI: 48.6-545.9 nmol/L and 180 (291.6 (15.8-567.5 nmol/L min. The difference in T-HDLP by condition was due to the significantly higher small-dense HDLP (T-HDLP-LB-HDL2b during HP versus HMF condition at 120 (mean difference: 452.6 (95% CI: 177.4-727.9 nmol/L and 180 (496.8 (263.1-730.6 nmol/L min. Area under the curve analysis showed that HP versus HMF condition led to significantly lower TG, non-HDLP, and very-low-density lipoprotein particles (VLDLP responses but significantly less favorable responses in LB-HDL2b particles, T-HDLP-LB-HDL2b, and LB-HDL2b/T-HDLP ratio.The HP meal led to lower TG, non-HDLP, and VLDLP but less favorable LB-HDL2b, small-dense HDLP, and LB-HDL2b/T-HDLP ratio responses versus a HMF meal. Further studies are needed to confirm these findings over multiple meals.
DEFF Research Database (Denmark)
Liu, Hongtai; Gao, Ya; Hu, Zhiyang
2016-01-01
Objectives The aim of this study was to assess the performance of noninvasively prenatal testing (NIPT) for fetal copy number variants (CNVs) in clinical samples, using a whole-genome sequencing method. Method A total of 919 archived maternal plasma samples with karyotyping/microarray results...... in the study. Ten false positive results and two false negative results were obtained. The sensitivity and specificity of detection deletions/duplications were 84.21% and 98.42%, respectively. Conclusion Whole-genome sequencing-based NIPT has high performance in detecting genome-wide CNVs, in particular > 10Mb...... CNVs using the current FCAPS algorithm. It is possible to implement the current method in NIPT to prenatally screening for fetal CNVs. Keywords...
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Michal R Schweiger
Full Text Available BACKGROUND: Cancer re-sequencing programs rely on DNA isolated from fresh snap frozen tissues, the preparation of which is combined with additional preservation efforts. Tissue samples at pathology departments are routinely stored as formalin-fixed and paraffin-embedded (FFPE samples and their use would open up access to a variety of clinical trials. However, FFPE preparation is incompatible with many down-stream molecular biology techniques such as PCR based amplification methods and gene expression studies. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated the sample quality requirements of FFPE tissues for massively parallel short-read sequencing approaches. We evaluated key variables of pre-fixation, fixation related and post-fixation processes that occur in routine medical service (e.g. degree of autolysis, duration of fixation and of storage. We also investigated the influence of tissue storage time on sequencing quality by using material that was up to 18 years old. Finally, we analyzed normal and tumor breast tissues using the Sequencing by Synthesis technique (Illumina Genome Analyzer, Solexa to simultaneously localize genome-wide copy number alterations and to detect genomic variations such as substitutions and point-deletions and/or insertions in FFPE tissue samples. CONCLUSIONS/SIGNIFICANCE: The application of second generation sequencing techniques on small amounts of FFPE material opens up the possibility to analyze tissue samples which have been collected during routine clinical work as well as in the context of clinical trials. This is in particular important since FFPE samples are amply available from surgical tumor resections and histopathological diagnosis, and comprise tissue from precursor lesions, primary tumors, lymphogenic and/or hematogenic metastases. Large-scale studies using this tissue material will result in a better prediction of the prognosis of cancer patients and the early identification of patients which
Drescher, U; Koschate, J; Schiffer, T; Schneider, S; Hoffmann, U
2017-06-01
The aim of the study was to compare the kinetics responses of heart rate (HR), pulmonary (V˙O2pulm) and predicted muscular (V˙O2musc) oxygen uptake between two different pseudo-random binary sequence (PRBS) work rate (WR) amplitudes both below anaerobic threshold. Eight healthy individuals performed two PRBS WR protocols implying changes between 30W and 80W and between 30W and 110W. HR and V˙O2pulm were measured beat-to-beat and breath-by-breath, respectively. V˙O2musc was estimated applying the approach of Hoffmann et al. (Eur J Appl Physiol 113: 1745-1754, 2013) considering a circulatory model for venous return and cross-correlation functions (CCF) for the kinetics analysis. HR and V˙O2musc kinetics seem to be independent of WR intensity (p>0.05). V˙O2pulm kinetics show prominent differences in the lag of the CCF maximum (39±9s; 31±4s; pkinetics remain unchanged. Copyright © 2017 Elsevier B.V. All rights reserved.
Energy Technology Data Exchange (ETDEWEB)
Coronel B, H.F.; Hernandez M, A.R.; Jimenez M, M.A. [Facultad de Fisica e Inteligencia Artificial, Universidad Veracruzana, A.P. 475, Xalapa, Veracruz (Mexico); Mora F, L.E. [CIMAT, A.P. 402, 36000 Guanajuato (Mexico)]. e-mail: hcoronel@uv.mx
2007-07-01
Empirical tests for pseudo random number generators based on the use of processes or physical models have been successfully used and are considered as complementary to theoretical tests of randomness. In this work a statistical methodology for evaluating the quality of pseudo random number generators is presented. The method is illustrated in the context of the so-called exponential decay process, using some pseudo random number generators commonly used in physics. (Author)
KinMutRF: a random forest classifier of sequence variants in the human protein kinase superfamily.
Pons, Tirso; Vazquez, Miguel; Matey-Hernandez, María Luisa; Brunak, Søren; Valencia, Alfonso; Izarzugaza, Jose Mg
2016-06-23
The association between aberrant signal processing by protein kinases and human diseases such as cancer was established long time ago. However, understanding the link between sequence variants in the protein kinase superfamily and the mechanistic complex traits at the molecular level remains challenging: cells tolerate most genomic alterations and only a minor fraction disrupt molecular function sufficiently and drive disease. KinMutRF is a novel random-forest method to automatically identify pathogenic variants in human kinases. Twenty six decision trees implemented as a random forest ponder a battery of features that characterize the variants: a) at the gene level, including membership to a Kinbase group and Gene Ontology terms; b) at the PFAM domain level; and c) at the residue level, the types of amino acids involved, changes in biochemical properties, functional annotations from UniProt, Phospho.ELM and FireDB. KinMutRF identifies disease-associated variants satisfactorily (Acc: 0.88, Prec:0.82, Rec:0.75, F-score:0.78, MCC:0.68) when trained and cross-validated with the 3689 human kinase variants from UniProt that have been annotated as neutral or pathogenic. All unclassified variants were excluded from the training set. Furthermore, KinMutRF is discussed with respect to two independent kinase-specific sets of mutations no included in the training and testing, Kin-Driver (643 variants) and Pon-BTK (1495 variants). Moreover, we provide predictions for the 848 protein kinase variants in UniProt that remained unclassified. A public implementation of KinMutRF, including documentation and examples, is available online ( http://kinmut2.bioinfo.cnio.es ). The source code for local installation is released under a GPL version 3 license, and can be downloaded from https://github.com/Rbbt-Workflows/KinMut2 . KinMutRF is capable of classifying kinase variation with good performance. Predictions by KinMutRF compare favorably in a benchmark with other state
Pittet, Vanessa; Phister, Trevor G.; Ziola, Barry
2013-01-01
Growth of specific lactic acid bacteria in beer leads to spoiled product and economic loss for the brewing industry. Microbial growth is typically inhibited by the combined stresses found in beer (e.g., ethanol, hops, low pH, minimal nutrients); however, certain bacteria have adapted to grow in this harsh environment. Considering little is known about the mechanisms used by bacteria to grow in and spoil beer, transcriptome sequencing was performed on a variant of the beer-spoilage organism Pediococcusclaussenii ATCC BAA-344T (Pc344-358). Illumina sequencing was used to compare the transcript levels in Pc344-358 growing mid-exponentially in beer to those in nutrient-rich MRS broth. Various operons demonstrated high gene expression in beer, several of which are involved in nutrient acquisition and overcoming the inhibitory effects of hop compounds. As well, genes functioning in cell membrane modification and biosynthesis demonstrated significantly higher transcript levels in Pc344-358 growing in beer. Three plasmids had the majority of their genes showing increased transcript levels in beer, whereas the two cryptic plasmids showed slightly decreased gene expression. Follow-up analysis of plasmid copy number in both growth environments revealed similar trends, where more copies of the three non-cryptic plasmids were found in Pc344-358 growing in beer. Transcriptome sequencing also enabled the addition of several genes to the P. claussenii ATCC BAA-344T genome annotation, some of which are putatively transcribed as non-coding RNAs. The sequencing results not only provide the first transcriptome description of a beer-spoilage organism while growing in beer, but they also highlight several targets for future exploration, including genes that may have a role in the general stress response of lactic acid bacteria. PMID:24040005
Directory of Open Access Journals (Sweden)
Scott Christopher J
2010-04-01
Full Text Available Abstract Background The DUB/USP17 subfamily of deubiquitinating enzymes were originally identified as immediate early genes induced in response to cytokine stimulation in mice (DUB-1, DUB-1A, DUB-2, DUB-2A. Subsequently we have identified a number of human family members and shown that one of these (DUB-3 is also cytokine inducible. We originally showed that constitutive expression of DUB-3 can block cell proliferation and more recently we have demonstrated that this is due to its regulation of the ubiquitination and activity of the 'CAAX' box protease RCE1. Results Here we demonstrate that the human DUB/USP17 family members are found on both chromosome 4p16.1, within a block of tandem repeats, and on chromosome 8p23.1, embedded within the copy number variable beta-defensin cluster. In addition, we show that the multiple genes observed in humans and other distantly related mammals have arisen due to the independent expansion of an ancestral sequence within each species. However, it is also apparent when sequences from humans and the more closely related chimpanzee are compared, that duplication events have taken place prior to these species separating. Conclusions The observation that the DUB/USP17 genes, which can influence cell growth and survival, have evolved from an unstable ancestral sequence which has undergone multiple and varied duplications in the species examined marks this as a unique family. In addition, their presence within the beta-defensin repeat raises the question whether they may contribute to the influence of this repeat on immune related conditions.
Biesecker, Barbara B; Lewis, Katie L; Umstead, Kendall L; Johnston, Jennifer J; Turbitt, Erin; Fishler, Kristen P; Patton, John H; Miller, Ilana M; Heidlebaugh, Alexis R; Biesecker, Leslie G
2018-01-22
A critical bottleneck in clinical genomics is the mismatch between large volumes of results and the availability of knowledgeable professionals to return them. To test whether a web-based platform is noninferior to a genetic counselor for educating patients about their carrier results from exome sequencing. A randomized noninferiority trial conducted in a longitudinal sequencing cohort at the National Institutes of Health from February 5, 2014, to December 16, 2016, was used to compare the web-based platform with a genetic counselor. Among the 571 eligible participants, 1 to 7 heterozygous variants were identified in genes that cause a phenotype that is recessively inherited. Surveys were administered after cohort enrollment, immediately following trial education, and 1 month and 6 months later to primarily healthy postreproductive participants who expressed interest in learning their carrier results. Both intention-to-treat and per-protocol analyses were applied. A web-based platform that integrated education on carrier results with personal test results was designed to directly parallel disclosure education by a genetic counselor. The sessions took a mean (SD) time of 21 (10.6), and 27 (9.3) minutes, respectively. The primary outcomes and noninferiority margins (δNI) were knowledge (0 to 8, δNI = -1), test-specific distress (0 to 30, δNI = +1), and decisional conflict (15 to 75, δNI = +6). After 462 participants (80.9%) provided consent and were randomized, all but 3 participants (n = 459) completed surveys following education and counseling; 398 (86.1%) completed 1-month surveys and 392 (84.8%) completed 6-month surveys. Participants were predominantly well-educated, non-Hispanic white, married parents; mean (SD) age was 63 (63.1) years and 246 (53.6%) were men. The web platform was noninferior to the genetic counselor on outcomes assessed at 1 and 6 months: knowledge (mean group difference, -0.18; lower limit of 97.5% CI, -0.63;
Hou, Gang; Miao, Yuan; Hu, Xue-Jun; Wang, Wei; Wang, Qiu-Yue; Wu, Guang-Ping; Wang, En-Hua; Kang, Jian
2016-03-01
Optimizing basic techniques in diagnostic bronchoscopy is important for improving medical services in developing countries. In this study, the optimal sequence of bronchial brushing relative to bronchial biopsy for lung cancer diagnosis was evaluated. A total of 420 patients with visible endobronchial tumors were prospectively and randomly enrolled in two groups: a pre-biopsy brushing group, receiving two brushings before biopsy; two brushings which performed afterwards; were set as self-control and compared with the pre-biopsy brushings as the intra-group comparison; and a post-biopsy brushing group, only receiving two brushings after biopsy, which were compared with the pre-biopsy brushings as the inter-group comparison. Diagnostic yield of brushing was compared before and after biopsy, and as well as for different tumor pathologies and bronchoscopic morphologies. The occurrence of treated bleeding which defined as bleeding needed further intervention with argon plasma coagulation and/or anti-coagulation drugs in two groups was also compared. Only patients with a definitive cytological or histological diagnosis of lung cancer based on bronchoscopy or other confirmatory techniques were included. Patients were excluded if they had submucosal lesions, extrinsic compressions, pulmonary metastasis of extrapulmonary malignancies or uncommon non-small cell lung carcinoma (NSCLC). A total of 362 patients who met the inclusion criteria were analyzed. Diagnostic yield for pre-biopsy brushing (49.2%, 88/179) was significantly higher than for post-biopsy brushing within the same pre-biopsy brushing group (31.8%, 57/179) (P=0.007) as the intra-group comparison, and significantly higher than for post-biopsy brushing in the post group (30.6%, 56/183) (Pcancer. In cases of endobronchial exophytic tumors, pre-biopsy brushing appears to be superior to post-biopsy brushing.
Rehmani, Rifat; LeBlanc, John C
2010-01-01
Background Although unintentional injuries are major causes of morbidity and mortality in less developed countries, they have received scant attention, and injury prevention policies and programs have just begun to be addressed systemically. Aims To reduce hazards associated with home injuries due to falls and ingestions through an injury prevention program administered by home visitors. Methods Non-blinded randomized controlled trial design of two interventions where one branch of the study ...
Michas, Georgios; Vallianatos, Filippos; Karakostas, Vassilios; Papadimitriou, Eleftheria; Sammonds, Peter
2014-05-01
Efpalion aftershock sequence occurred in January 2010, when an M=5.5 earthquake was followed four days later by another strong event (M=5.4) and numerous aftershocks (Karakostas et al., 2012). This activity interrupted a 15 years period of low to moderate earthquake occurrence in Corinth rift, where the last major event was the 1995 Aigion earthquake (M=6.2). Coulomb stress analysis performed in previous studies (Karakostas et al., 2012; Sokos et al., 2012; Ganas et al., 2013) indicated that the second major event and most of the aftershocks were triggered due to stress transfer. The aftershocks production rate decays as a power-law with time according to the modified Omori law (Utsu et al., 1995) with an exponent larger than one for the first four days, while after the occurrence of the second strong event the exponent turns to unity. We consider the earthquake sequence as a point process in time and space and study its spatiotemporal evolution considering a Continuous Time Random Walk (CTRW) model with a joint probability density function of inter-event times and jumps between the successive earthquakes (Metzler and Klafter, 2000). Jump length distribution exhibits finite variance, whereas inter-event times scale as a q-generalized gamma distribution (Michas et al., 2013) with a long power-law tail. These properties are indicative of a subdiffusive process in terms of CTRW. Additionally, the mean square displacement of aftershocks is constant with time after the occurrence of the first event, while it changes to a power-law with exponent close to 0.15 after the second major event, illustrating a slow diffusive process. During the first four days aftershocks cluster around the epicentral area of the second major event, while after that and taking as a reference the second event, the aftershock zone is migrating slowly with time to the west near the epicentral area of the first event. This process is much slower from what would be expected from normal diffusion, a
Liu, Yu; Gong, Li-Ping; Dong, Xiao-Li; Liu, Hong-Gang
2013-06-01
The aim of this study was to determine the translocation and copy number change of the C-MYC gene in patients with laryngeal dysplasia and laryngeal squamous cell carcinoma (LSCC), and to evaluate the prevalence of such expression in relation to the normal-dysplasia-carcinoma sequence. Fluorescent in situ hybridization (FISH) was applied on formalin-fixed paraffin-embedded blocks of 93 laryngeal lesion specimens (14 normal epithelium, 15 mild dysplasia, 18 moderate dysplasia, 16 severe dysplasia, 9 carcinoma in situ, and 21 invasive carcinoma). C-MYC translocation was not observed in all laryngeal tissue. The high frequency for C-MYC copy-number increased (100%) in invasive carcinoma: 57.14% amplifications and 42.86% gains, and the positive rate of C-MYC amplification and copy-number change increased with the increasing severity of laryngeal lesions (P < 0.0001). The results suggest that C-MYC may be activated by gain/amplification in LSCC and precancerous lesions. Thus, C-MYC may play an important role in promoting LSCC progression, and early FISH detection of C-MYC may be exploited to set a screening test for laryngeal dysplasia. Copyright © 2012 Wiley Periodicals, Inc.
Garcia, S A L; Van der Lee, T A J; Ferreira, C F; Te Lintel Hekkert, B; Zapater, M-F; Goodwin, S B; Guzmán, M; Kema, G H J; Souza, M T
2010-11-09
We searched the genome of Mycosphaerella fijiensis for molecular markers that would allow population genetics analysis of this plant pathogen. M. fijiensis, the causal agent of banana leaf streak disease, also known as black Sigatoka, is the most devastating pathogen attacking bananas (Musa spp). Recently, the entire genome sequence of M. fijiensis became available. We screened this database for VNTR markers. Forty-two primer pairs were selected for validation, based on repeat type and length and the number of repeat units. Five VNTR markers showing multiple alleles were validated with a reference set of isolates from different parts of the world and a population from a banana plantation in Costa Rica. Polymorphism information content values varied from 0.6414 to 0.7544 for the reference set and from 0.0400 and 0.7373 for the population set. Eighty percent of the polymorphism information content values were above 0.60, indicating that the markers are highly informative. These markers allowed robust scoring of agarose gels and proved to be useful for variability and population genetics studies. In conclusion, the strategy we developed to identify and validate VNTR markers is an efficient means to incorporate markers that can be used for fungicide resistance management and to develop breeding strategies to control banana black leaf streak disease. This is the first report of VNTR-minisatellites from the M. fijiensis genome sequence.
Lou, Haiyi; Lu, Yan; Lu, Dongsheng; Fu, Ruiqing; Wang, Xiaoji; Feng, Qidi; Wu, Sijie; Yang, Yajun; Li, Shilin; Kang, Longli; Guan, Yaqun; Hoh, Boon-Peng; Chung, Yeun-Jun; Jin, Li; Su, Bing; Xu, Shuhua
2015-07-02
Tibetan high-altitude adaptation (HAA) has been studied extensively, and many candidate genes have been reported. Subsequent efforts targeting HAA functional variants, however, have not been that successful (e.g., no functional variant has been suggested for the top candidate HAA gene, EPAS1). With WinXPCNVer, a method developed in this study, we detected in microarray data a Tibetan-enriched deletion (TED) carried by 90% of Tibetans; 50% were homozygous for the deletion, whereas only 3% carried the TED and 0% carried the homozygous deletion in 2,792 worldwide samples (p hemoglobin. It was also in complete LD with the 5-SNP motif, which was suspected to be introgressed from Denisovans, but the deletion itself was absent from the Denisovan sequence. Correspondingly, we detected that footprints of positive selection for the TED occurred 12,803 (95% confidence interval = 12,075-14,725) years ago. We further whole-genome deep sequenced (>60×) seven Tibetans and verified the TED but failed to identify any other copy-number variations with comparable patterns, giving this TED top priority for further study. We speculate that the specific patterns of the TED resulted from its own functionality in HAA of Tibetans or LD with a functional variant of EPAS1. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Zhang, Y; Song, Y; Cao, H; Mo, X; Yang, H; Wang, J; Lu, Z; Zhang, T
2017-03-01
HLA-DRB3, DRB4 and DRB5 (DRB3/4/5) are paralogues of HLA-DRB1. They have important roles in transplantation and have been reported to be related to many diseases. HLA typing methods for DRB3/4/5 based on NGS data have many limitations now, such as need of polymerase chain reaction (PCR) or low accuracy. We present a HLA typing method for DRB3/4/5 based on read mapping and haplotype assembly from NGS data. Also, copy number of DRB3/4/5 is determined by a k-means clustering method according to ratio of sequencing depth between DRB3/4/5 and DRB1. We achieved 100%, 100%, 100% accuracy on simulated data and 95.88%, 98.89%, 99.34% accuracy on MHC capture Illumina sequencing data at 4-digit resolution with 30-fold coverage for DRB3/4/5 separately. We also explored the DRB3/4/5 profiles in five continental populations through low coverage WGS data generated by the 1000 Genome Project. We found that frequency of DRB4 in African were significantly lower than that in all other populations. Our method for DRB3/4/5 typing has high accuracy. It is a good supplement to regular HLA typing and could help in disease studies, medical applications and human population diversity studies. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Kader, Tanjina; Goode, David L; Wong, Stephen Q; Connaughton, Jacquie; Rowley, Simone M; Devereux, Lisa; Byrne, David; Fox, Stephen B; Mir Arnau, Gisela; Tothill, Richard W; Campbell, Ian G; Gorringe, Kylie L
2016-11-15
Unlocking clinically translatable genomic information, including copy number alterations (CNA), from formalin-fixed paraffin-embedded (FFPE) tissue is challenging due to low yields and degraded DNA. We describe a robust, cost-effective low-coverage whole genome sequencing (LC WGS) method for CNA detection using 5 ng of FFPE-derived DNA. CN profiles using 100 ng or 5 ng input DNA were highly concordant and comparable with molecular inversion probe (MIP) array profiles. LC WGS improved CN profiles of samples that performed poorly using MIP arrays. Our technique enables identification of driver and prognostic CNAs in archival patient samples previously deemed unsuitable for genomic analysis due to DNA limitations.
Mendoza, C.; Bautista, M. A.; Palmeri, P.; Quinet, P.; Witthoeft, M. C.; Kallman, T. R.
2017-08-01
Context. We are concerned with improving the diagnostic potential of the K lines and edges of elements with low cosmic abundances, namely F, Na, P, Cl, K, Sc, Ti, V, Cr, Mn, Co, Cu, and Zn, that are observed in the X-ray spectra of supernova remnants, galaxy clusters, and accreting black holes and neutron stars. Aims: Since accurate photoabsorption and photoionization cross sections are needed in their spectral models, they have been computed for isoelectronic sequences with electron number 12 ≤ N ≤ 18 using a multi-channel method. Methods: Target representations are obtained with the atomic structure code autostructure, and ground-state cross sections are computed with the Breit-Pauli R-matrix method (bprm) in intermediate coupling, including damping (radiative and Auger) effects. Results: Following the findings in our earlier work on sequences with 2 ≤ N ≤ 11, the contributions from channels associated with the 2s-hole [2s] μ target configurations and those containing 3d orbitals are studied in the Mg (N = 12) and Ar (N = 18) isoelectronic sequences. Cross sections for the latter ions are also calculated in the isolated-resonance approximation as implemented in autostructure and compared with bprm to test their accuracy. Conclusions: It is confirmed that the collisional channels associated with the [2s] μ target configurations must be taken into account owing to significant increases in the monotonic background cross section between the L and K edges. Target configurations with 3d orbitals give rise to fairly conspicuous unresolved transition arrays in the L-edge region, but to a much lesser extent in the K-edge that is our main concern; therefore, they have been neglected throughout owing to their computationally intractable channel inventory, thus allowing the computation of cross sections for all the ions with 12 ≤ N ≤ 18 in intermediate coupling with bprm. We find that the isolated-resonance approximations performs satisfactorily and will be our
Siegel, Z.; Siegel, Edward Carl-Ludwig
2011-03-01
RANDOMNESS of Numbers cognitive-semantics DEFINITION VIA Cognition QUERY: WHAT???, NOT HOW?) VS. computer-``science" mindLESS number-crunching (Harrel-Sipser-...) algorithmics Goldreich "PSEUDO-randomness"[Not.AMS(02)] mea-culpa is ONLY via MAXWELL-BOLTZMANN CLASSICAL-STATISTICS(NOT FDQS!!!) "hot-plasma" REPULSION VERSUS Newcomb(1881)-Weyl(1914;1916)-Benford(1938) "NeWBe" logarithmic-law digit-CLUMPING/ CLUSTERING NON-Randomness simple Siegel[AMS Joint.Mtg.(02)-Abs. # 973-60-124] algebraic-inversion to THE QUANTUM and ONLY BEQS preferentially SEQUENTIALLY lower-DIGITS CLUMPING/CLUSTERING with d = 0 BEC, is ONLY VIA Siegel-Baez FUZZYICS=CATEGORYICS (SON OF TRIZ)/"Category-Semantics"(C-S), latter intersection/union of Lawvere(1964)-Siegel(1964)] category-theory (matrix: MORPHISMS V FUNCTORS) "+" cognitive-semantics'' (matrix: ANTONYMS V SYNONYMS) yields Siegel-Baez FUZZYICS=CATEGORYICS/C-S tabular list-format matrix truth-table analytics: MBCS RANDOMNESS TRUTH/EMET!!!
Kundig, François; Staines, Anthony; Kinge, Thompson; Perneger, Thomas V
2011-11-01
In self-completed surveys, anonymous questionnaires are sometimes numbered so as to avoid sending reminders to initial nonrespondents. This number may be perceived as a threat to confidentiality by some respondents, which may reduce the response rate, or cause social desirability bias. In this study, we evaluated whether using nonnumbered vs. numbered questionnaires influenced the response rate and the response content. During a patient safety culture survey, we randomized participants into two groups: one received an anonymous nonnumbered questionnaire and the other a numbered questionnaire. We compared the survey response rates and distributions of the responses for the 42-questionnaire items across the two groups. Response rates were similar in the two groups (nonnumbered, 75.2%; numbered, 72.8%; difference, 2.4%; P=0.28). Five of the 42 questions had statistically significant differences in distributions, but these differences were small. Unexpectedly, in all five instances, the patient safety culture ratings were more favorable in the nonnumbered group. Numbering of mailed questionnaires had no impact on the response rate. Numbering influenced significantly the response content of several items, but these differences were small and ran against the hypothesis of social desirability bias. Copyright © 2011 Elsevier Inc. All rights reserved.
Fischer, Martin; Elm, Matthias T.; Kato, Hiroaki; Sakita, Shinya; Hara, Shinjiro; Klar, Peter J.
2015-10-01
The temporal dependence of the resistance of MnAs nanocluster arrangements grown by selective-area metal-organic vapor-phase epitaxy is investigated at different temperatures. The resistance of such arrangements exhibits random telegraph noise with jumps between discrete resistance levels. The effect is attributed to thermally activated switching of the magnetic domain structure resulting in alterations of spin-dependent scattering between the MnAs clusters of the arrangements. The behavior can be qualitatively understood by a simple model in which it is assumed that the nanocluster arrangement consists of three domains in accordance with investigations by magnetic force microscopy. The magnetizations of the outer larger domains remain fixed, whereas the magnetization of a smaller intermediate domain (or domain wall) exhibits thermally activated switching between local minima of its energy landscape. The results of the model indicate that the time scale of an actual switching event of the entire intermediate domain comprises the nucleation of a seed domain consisting of a few thousand Mn spins followed by the transformation of the entire domain by domain-wall motion in order to reorient its magnetization.
Ferguson, Naola M; Hepp, Diego; Sun, Shulei; Ikuta, Nilo; Levisohn, Sharon; Kleven, Stanley H; García, Maricarmen
2005-06-01
A total of 67 Mycoplasma gallisepticum field isolates from the USA, Israel and Australia, and 10 reference strains, were characterized by gene-targeted sequencing (GTS) analysis of portions of the putative cytadhesin pvpA gene, the cytadhesin gapA gene, the cytadhesin mgc2 gene, and an uncharacterized hypothetical surface lipoprotein-encoding gene designated genome coding DNA sequence (CDS) MGA_0319. The regions of the surface-protein-encoding genes targeted in this analysis were found to be stable within a strain, after sequencing different in vitro passages of M. gallisepticum reference strains. Gene sequences were first analysed on the basis of gene size polymorphism. The pvpA and mgc2 genes are characterized by the presence of different nucleotide insertions/deletions. However, differentiation of isolates based solely on pvpA/mgc2 PCR size polymorphism was not found to be a reliable method to differentiate among M. gallisepticum isolates. On the other hand, GTS analysis based on the nucleotide sequence identities of individual and multiple genes correlated with epidemiologically linked isolates and with random amplified polymorphic DNA (RAPD) analysis. GTS analysis of individual genes, gapA, MGA_0319, mgc2 and pvpA, identified 17, 16, 20 and 22 sequence types, respectively. GTS analysis using multiple gene sequences mgc2/pvpa and gapA/MGA_0319/mgc2/pvpA identified 38 and 40 sequence types, respectively. GTS of multiple surface-protein-encoding genes showed better discriminatory power than RAPD analysis, which identified 36 pattern types from the same panel of M. gallisepticum strains. These results are believed to provide the first evidence that typing of M. gallisepticum isolates by GTS analysis of surface-protein genes is a sensitive and reproducible typing method and will allow rapid global comparisons between laboratories.
Radwan, Ahmed Gomaa
2014-06-18
This paper presents a digital implementation of a 3rd order chaotic system using the Euler approximation. Short-term predictability is studied in relation to system precision, Euler step size and attractor size and optimal parameters for maximum performance are derived. Defective bits from the native chaotic output are neglected and the remaining pass the NIST SP. 800-22 tests without post-processing. The resulting optimized pseudorandom number generator has throughput up to 17.60 Gbits/s for a 64-bit design experimentally verified on a Xilinx Virtex 4 FPGA with logic utilization less than 1.85%.
Gamble, Tony; Coryell, Jessi; Ezaz, Tariq; Lynch, Joshua; Scantlebury, Daniel P; Zarkower, David
2015-05-01
Sex chromosomes have evolved many times in animals and studying these replicate evolutionary "experiments" can help broaden our understanding of the general forces driving the origin and evolution of sex chromosomes. However this plan of study has been hindered by the inability to identify the sex chromosome systems in the large number of species with cryptic, homomorphic sex chromosomes. Restriction site-associated DNA sequencing (RAD-seq) is a critical enabling technology that can identify the sex chromosome systems in many species where traditional cytogenetic methods have failed. Using newly generated RAD-seq data from 12 gecko species, along with data from the literature, we reinterpret the evolution of sex-determining systems in lizards and snakes and test the hypothesis that sex chromosomes can routinely act as evolutionary traps. We uncovered between 17 and 25 transitions among gecko sex-determining systems. This is approximately one-half to two-thirds of the total number of transitions observed among all lizards and snakes. We find support for the hypothesis that sex chromosome systems can readily become trap-like and show that adding even a small number of species from understudied clades can greatly enhance hypothesis testing in a model-based phylogenetic framework. RAD-seq will undoubtedly prove useful in evaluating other species for male or female heterogamety, particularly the majority of fish, amphibian, and reptile species that lack visibly heteromorphic sex chromosomes, and will significantly accelerate the pace of biological discovery. © The Author 2015. 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.
Fully digital 1-D, 2-D and 3-D multiscroll chaos as hardware pseudo random number generators
Mansingka, Abhinav S.
2012-10-07
This paper introduces the first fully digital implementation of 1-D, 2-D and 3-D multiscroll chaos using the sawtooth nonlinearity in a 3rd order ODE with the Euler approximation. Systems indicate chaotic behaviour through phase space boundedness and positive Lyapunov exponent. Low-significance bits form a PRNG and pass all tests in the NIST SP. 800-22 suite without post-processing. Real-time control of the number of scrolls allows distinct output streams with 2-D and 3-D multiscroll chaos enabling greater controllability. The proposed PRNGs are experimentally verified on a Xilinx Virtex 4 FPGA with logic utilization less than 1.25%, throughput up to 5.25 Gbits/s and up to 512 distinct output streams with low cross-correlation.
Cohen, Dale J; Quinlan, Philip T
2016-12-01
How do people derive meaning from numbers? Here, we instantiate the primary theories of numerical representation in computational models and compare simulated performance to human data. Specifically, we fit simulated data to the distributions for correct and incorrect responses, as well as the pattern of errors made, in a traditional "relative quantity" task. The results reveal that no current theory of numerical representation can adequately account for the data without additional assumptions. However, when we introduce repeated, error-prone sampling of the stimulus (e.g., Cohen, 2009) superior fits are achieved when the underlying representation of integers reflects linear spacing with constant variance. These results provide new insights into (i) the detailed nature of mental numerical representation, and, (ii) general perceptual processes implemented by the human visual system. Copyright © 2016 Elsevier Inc. All rights reserved.
Hinedi, S.; Polydoros, A.
1988-01-01
The authors present and analyze a frequency-noncoherent two-lag autocorrelation statistic for the wideband detection of random BPSK signals in noise-plus-random-multitone interference. It is shown that this detector is quite robust to the presence or absence of interference and its specific parameter values, contrary to the case of an energy detector. The rule assumes knowledge of the data rate and the active scenario under H0. It is concluded that the real-time autocorrelation domain and its samples (lags) are a viable approach for detecting random signals in dense environments.
Zhang, Xianghong; Müller, Sebastian; Möller, Michael; Huse, Klaus; Taudien, Stefan; Book, Malte; Stuber, Frank; Platzer, Matthias; Groth, Marco
2014-01-24
The copy number variation (CNV) in beta-defensin genes (DEFB) on human chromosome 8p23 has been proposed to contribute to the phenotypic differences in inflammatory diseases. However, determination of exact DEFB CN is a major challenge in association studies. Quantitative real-time PCR (qPCR), paralog ratio tests (PRT) and multiplex ligation-dependent probe amplification (MLPA) have been extensively used to determine DEFB CN in different laboratories, but inter-method inconsistencies were observed frequently. In this study we asked which one is superior among the three methods for DEFB CN determination. We developed a clustering approach for MLPA and PRT to statistically correlate data from a single experiment. Then we compared qPCR, a newly designed PRT and MLPA for DEFB CN determination in 285 DNA samples. We found MLPA had the best convergence and clustering results of the raw data and the highest call rate. In addition, the concordance rates between MLPA or PRT and qPCR (32.12% and 37.99%, respectively) were unacceptably low with underestimated CN by qPCR. Concordance rate between MLPA and PRT (90.52%) was high but PRT systematically underestimated CN by one in a subset of samples. In these samples a sequence variant which caused complete PCR dropout of the respective DEFB cluster copies was found in one primer binding site of one of the targeted paralogous pseudogenes. MLPA is superior to PRT and even more to qPCR for DEFB CN determination. Although the applied PRT provides in most cases reliable results, such a test is particularly sensitive to low-frequency sequence variations preferably accumulating in loci like pseudogenes which are most likely not under selective pressure. In the light of the superior performance of multiplex assays, the drawbacks of such single PRTs could be overcome by combining more test markers.
Yamamoto, Toshiyuki; Shimojima, Keiko; Ondo, Yumiko; Imai, Katsumi; Chong, Pin Fee; Kira, Ryutaro; Amemiya, Mitsuhiro; Saito, Akira; Okamoto, Nobuhiko
2016-01-01
Next-generation sequencing (NGS) is widely used for the detection of disease-causing nucleotide variants. The challenges associated with detecting copy number variants (CNVs) using NGS analysis have been reported previously. Disease-related exome panels such as Illumina TruSight One are more cost-effective than whole-exome sequencing (WES) because of their selective target regions (~21% of the WES). In this study, CNVs were analyzed using data extracted through a disease-related exome panel analysis and the eXome Hidden Markov Model (XHMM). Samples from 61 patients with undiagnosed developmental delays and 52 healthy parents were included in this study. In the preliminary study to validate the constructed XHMM system (microarray-first approach), 34 patients who had previously been analyzed by chromosomal microarray testing were used. Among the five CNVs larger than 200 kb that were considered as non-pathogenic CNVs and were used as positive controls, four CNVs was successfully detected. The system was subsequently used to analyze different samples from 27 patients (NGS-first approach); 2 of these patients were successfully diagnosed as having pathogenic CNVs (an unbalanced translocation der(5)t(5;14) and a 16p11.2 duplication). These diagnoses were re-confirmed by chromosomal microarray testing and/or fluorescence in situ hybridization. The NGS-first approach generated no false-negative or false-positive results for pathogenic CNVs, indicating its high sensitivity and specificity in detecting pathogenic CNVs. The results of this study show the possible clinical utility of pathogenic CNV screening using disease-related exome panel analysis and XHMM.
DEFF Research Database (Denmark)
Kjærgaard, Magnus; Poulsen, Flemming Martin
2011-01-01
. The contributions from the neighboring residues are typically removed by using neighbor correction factors determined based on each residue's effect on glycine chemical shifts. Due to its unusual conformational freedom, glycine may be particularly unrepresentative for the remaining residue types. In this study, we......Random coil chemical shifts are necessary for secondary chemical shift analysis, which is the main NMR method for identification of secondary structure in proteins. One of the largest challenges in the determination of random coil chemical shifts is accounting for the effect of neighboring residues...... use random coil peptides containing glutamine instead of glycine to determine the random coil chemical shifts and the neighbor correction factors. The resulting correction factors correlate to changes in the populations of the major wells in the Ramachandran plot, which demonstrates that changes...
Directory of Open Access Journals (Sweden)
Joop eHox
2014-02-01
Full Text Available Cluster randomized trials assess the effect of an intervention that is carried out at the group or cluster level. Ajzen’s theory of planned behaviour is often used to model the effect of the intervention as an indirect effect mediated in turn by attitude, norms and behavioural intention. Structural equation modelling (SEM is the technique of choice to estimate indirect effects and their significance. However, this is a large sample technique, and its application in a cluster randomized trial assumes a relatively large number of clusters. In practice, the number of clusters in these studies tends to be relatively small, e.g. much less than fifty. This study uses simulation methods to find the lowest number of clusters needed when multilevel SEM is used to estimate the indirect effect. Maximum likelihood estimation is compared to Bayesian analysis, with the central quality criteria being accuracy of the point estimate and the confidence interval. We also investigate the power of the test for the indirect effect. We conclude that Bayes estimation works well with much smaller cluster level sample sizes such as 20 cases than maximum likelihood estimation; although the bias is larger the coverage is much better. When only 5 to 10 clusters are available per treatment condition even with Bayesian estimation problems occur.
Diaz, Francisco J; Berg, Michel J; Krebill, Ron; Welty, Timothy; Gidal, Barry E; Alloway, Rita; Privitera, Michael
2013-12-01
Due to concern and debate in the epilepsy medical community and to the current interest of the US Food and Drug Administration (FDA) in revising approaches to the approval of generic drugs, the FDA is currently supporting ongoing bioequivalence studies of antiepileptic drugs, the EQUIGEN studies. During the design of these crossover studies, the researchers could not find commercial or non-commercial statistical software that quickly allowed computation of sample sizes for their designs, particularly software implementing the FDA requirement of using random-effects linear models for the analyses of bioequivalence studies. This article presents tables for sample-size evaluations of average bioequivalence studies based on the two crossover designs used in the EQUIGEN studies: the four-period, two-sequence, two-formulation design, and the six-period, three-sequence, three-formulation design. Sample-size computations assume that random-effects linear models are used in bioequivalence analyses with crossover designs. Random-effects linear models have been traditionally viewed by many pharmacologists and clinical researchers as just mathematical devices to analyze repeated-measures data. In contrast, a modern view of these models attributes an important mathematical role in theoretical formulations in personalized medicine to them, because these models not only have parameters that represent average patients, but also have parameters that represent individual patients. Moreover, the notation and language of random-effects linear models have evolved over the years. Thus, another goal of this article is to provide a presentation of the statistical modeling of data from bioequivalence studies that highlights the modern view of these models, with special emphasis on power analyses and sample-size computations.
Mansingka, Abhinav S.
2014-06-18
This paper introduces fully digital implementations of four di erent systems in the 3rd order jerk-equation based chaotic family using the Euler approximation. The digitization approach enables controllable chaotic systems that reliably provide sinusoidal or chaotic output based on a selection input. New systems are introduced, derived using logical and arithmetic operations between two system implementations of different bus widths, with up to 100x higher maximum Lyapunov exponent than the original jerkequation based chaotic systems. The resulting chaotic output is shown to pass the NIST sp. 800-22 statistical test suite for pseudorandom number generators without post-processing by only eliminating the statistically defective bits. The systems are designed in Verilog HDL and experimentally verified on a Xilinx Virtex 4 FPGA for a maximum throughput of 15.59 Gbits/s for the native chaotic output and 8.77 Gbits/s for the resulting pseudo-random number generators.
Directory of Open Access Journals (Sweden)
Hochul Lee
2017-05-01
Full Text Available A true random number generator based on perpendicularly magnetized voltage-controlled magnetic tunnel junction devices (MRNG is presented. Unlike MTJs used in memory applications where a stable bit is needed to store information, in this work, the MTJ is intentionally designed with small perpendicular magnetic anisotropy (PMA. This allows one to take advantage of the thermally activated fluctuations of its free layer as a stochastic noise source. Furthermore, we take advantage of the voltage dependence of anisotropy to temporarily change the MTJ state into an unstable state when a voltage is applied. Since the MTJ has two energetically stable states, the final state is randomly chosen by thermal fluctuation. The voltage controlled magnetic anisotropy (VCMA effect is used to generate the metastable state of the MTJ by lowering its energy barrier. The proposed MRNG achieves a high throughput (32 Gbps by implementing a 64×64 MTJ array into CMOS circuits and executing operations in a parallel manner. Furthermore, the circuit consumes very low energy to generate a random bit (31.5 fJ/bit due to the high energy efficiency of the voltage-controlled MTJ switching.
Lee, Hochul; Ebrahimi, Farbod; Amiri, Pedram Khalili; Wang, Kang L.
2017-05-01
A true random number generator based on perpendicularly magnetized voltage-controlled magnetic tunnel junction devices (MRNG) is presented. Unlike MTJs used in memory applications where a stable bit is needed to store information, in this work, the MTJ is intentionally designed with small perpendicular magnetic anisotropy (PMA). This allows one to take advantage of the thermally activated fluctuations of its free layer as a stochastic noise source. Furthermore, we take advantage of the voltage dependence of anisotropy to temporarily change the MTJ state into an unstable state when a voltage is applied. Since the MTJ has two energetically stable states, the final state is randomly chosen by thermal fluctuation. The voltage controlled magnetic anisotropy (VCMA) effect is used to generate the metastable state of the MTJ by lowering its energy barrier. The proposed MRNG achieves a high throughput (32 Gbps) by implementing a 64 ×64 MTJ array into CMOS circuits and executing operations in a parallel manner. Furthermore, the circuit consumes very low energy to generate a random bit (31.5 fJ/bit) due to the high energy efficiency of the voltage-controlled MTJ switching.
Directory of Open Access Journals (Sweden)
Maria Giné-Garriga
Full Text Available Effective promotion of exercise could result in substantial savings in healthcare cost expenses in terms of direct medical costs, such as the number of medical appointments. However, this is hampered by our limited knowledge of how to achieve sustained increases in physical activity.To assess the effectiveness of a Primary Health Care (PHC based physical activity program in reducing the total number of visits to the healthcare center among inactive patients, over a 15-month period.Randomized controlled trial.Three hundred and sixty-two (n = 362 inactive patients suffering from at least one chronic condition were included. One hundred and eighty-three patients (n = 183; mean (SD; 68.3 (8.8 years; 118 women were randomly allocated to the physical activity program (IG. One hundred and seventy-nine patients (n = 179; 67.2 (9.1 years; 106 women were allocated to the control group (CG. The IG went through a three-month standardized physical activity program led by physical activity specialists and linked to community resources.The total number of medical appointments to the PHC, during twelve months before and after the program, was registered. Self-reported health status (SF-12 version 2 was assessed at baseline (month 0, at the end of the intervention (month 3, and at 12 months follow-up after the end of the intervention (month 15.The IG had a significantly reduced number of visits during the 12 months after the intervention: 14.8 (8.5. The CG remained about the same: 18.2 (11.1 (P = .002.Our findings indicate that a 3-month physical activity program linked to community resources is a short-duration, effective and sustainable intervention in inactive patients to decrease rates of PHC visits.ClinicalTrials.gov NCT00714831.
Autonomous Byte Stream Randomizer
Paloulian, George K.; Woo, Simon S.; Chow, Edward T.
2013-01-01
Net-centric networking environments are often faced with limited resources and must utilize bandwidth as efficiently as possible. In networking environments that span wide areas, the data transmission has to be efficient without any redundant or exuberant metadata. The Autonomous Byte Stream Randomizer software provides an extra level of security on top of existing data encryption methods. Randomizing the data s byte stream adds an extra layer to existing data protection methods, thus making it harder for an attacker to decrypt protected data. Based on a generated crypto-graphically secure random seed, a random sequence of numbers is used to intelligently and efficiently swap the organization of bytes in data using the unbiased and memory-efficient in-place Fisher-Yates shuffle method. Swapping bytes and reorganizing the crucial structure of the byte data renders the data file unreadable and leaves the data in a deconstructed state. This deconstruction adds an extra level of security requiring the byte stream to be reconstructed with the random seed in order to be readable. Once the data byte stream has been randomized, the software enables the data to be distributed to N nodes in an environment. Each piece of the data in randomized and distributed form is a separate entity unreadable on its own right, but when combined with all N pieces, is able to be reconstructed back to one. Reconstruction requires possession of the key used for randomizing the bytes, leading to the generation of the same cryptographically secure random sequence of numbers used to randomize the data. This software is a cornerstone capability possessing the ability to generate the same cryptographically secure sequence on different machines and time intervals, thus allowing this software to be used more heavily in net-centric environments where data transfer bandwidth is limited.
Nonquadratic Variation of the Blum Blum Shub Pseudorandom Number Generator
2016-09-01
the use of random numbers. For this rea- son, cryptographers design pseudorandom number generators (PRNG) as a method of generating random numbers...fails the block frequency test, as it is clearly not random . 3.3.3 Runs Test A run is defined as a series of either 1’s or 0’s in a row. The purpose of...that would be expected of a random sequence. The NIST standard uses three common block sizes for this test, M = 8, 128, and 10, 000. The test divides
Ren Jian
2004-01-01
Pseudo-random sequence with good correlation property and large linear span is widely used in code division multiple access (CDMA) communication systems and cryptology for reliable and secure information transmission. In this paper, sequences with long period, large complexity, balance statistics, and low cross-correlation property are constructed from the addition of m -sequences with pairwise-prime linear spans (AMPLS). Using m -sequences as building blocks, the proposed method proved to...
Haider, Nadia
2017-01-01
Investigation of genetic variation and phylogenetic relationships among date palm (Phoenix dactylifera L.) cultivars is useful for their conservation and genetic improvement. Various molecular markers such as restriction fragment length polymorphisms (RFLPs), simple sequence repeat (SSR), representational difference analysis (RDA), and amplified fragment length polymorphism (AFLP) have been developed to molecularly characterize date palm cultivars. PCR-based markers random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) are powerful tools to determine the relatedness of date palm cultivars that are difficult to distinguish morphologically. In this chapter, the principles, materials, and methods of RAPD and ISSR techniques are presented. Analysis of data generated from these two techniques and the use of these data to reveal phylogenetic relationships among date palm cultivars are also discussed.
Rahbaralam, Maryam; Fernàndez-Garcia, Daniel; Sanchez-Vila, Xavier
2015-12-01
Random walk particle tracking methods are a computationally efficient family of methods to solve reactive transport problems. While the number of particles in most realistic applications is in the order of 106-109, the number of reactive molecules even in diluted systems might be in the order of fractions of the Avogadro number. Thus, each particle actually represents a group of potentially reactive molecules. The use of a low number of particles may result not only in loss of accuracy, but also may lead to an improper reproduction of the mixing process, limited by diffusion. Recent works have used this effect as a proxy to model incomplete mixing in porous media. In this work, we propose using a Kernel Density Estimation (KDE) of the concentrations that allows getting the expected results for a well-mixed solution with a limited number of particles. The idea consists of treating each particle as a sample drawn from the pool of molecules that it represents; this way, the actual location of a tracked particle is seen as a sample drawn from the density function of the location of molecules represented by that given particle, rigorously represented by a kernel density function. The probability of reaction can be obtained by combining the kernels associated to two potentially reactive particles. We demonstrate that the observed deviation in the reaction vs time curves in numerical experiments reported in the literature could be attributed to the statistical method used to reconstruct concentrations (fixed particle support) from discrete particle distributions, and not to the occurrence of true incomplete mixing. We further explore the evolution of the kernel size with time, linking it to the diffusion process. Our results show that KDEs are powerful tools to improve computational efficiency and robustness in reactive transport simulations, and indicates that incomplete mixing in diluted systems should be modeled based on alternative mechanistic models and not on a
Directory of Open Access Journals (Sweden)
Guziolowski Carito
2007-09-01
Full Text Available Abstract Background: We present the N-map method, a pairwise and asymmetrical approach which allows us to compare sequences by taking into account evolutionary events that produce shuffled, reversed or repeated elements. Basically, the optimal N-map of a sequence s over a sequence t is the best way of partitioning the first sequence into N parts and placing them, possibly complementary reversed, over the second sequence in order to maximize the sum of their gapless alignment scores. Results: We introduce an algorithm computing an optimal N-map with time complexity O (|s| × |t| × N using O (|s| × |t| × N memory space. Among all the numbers of parts taken in a reasonable range, we select the value N for which the optimal N-map has the most significant score. To evaluate this significance, we study the empirical distributions of the scores of optimal N-maps and show that they can be approximated by normal distributions with a reasonable accuracy. We test the functionality of the approach over random sequences on which we apply artificial evolutionary events. Practical Application: The method is illustrated with four case studies of pairs of sequences involving non-standard evolutionary events.
Mycosphaerella fijiensis, the causal agent of banana leaf streak disease (commonly known as black Sigatoka), is the most devastating pathogen attacking bananas (Musa spp). Recently the whole genome sequence of M. fijiensis became available. This sequence was screened for the presence of Variable Num...
Giorgio, Elisa; Ciolfi, Andrea; Biamino, Elisa; Caputo, Viviana; Di Gregorio, Eleonora; Belligni, Elga Fabia; Calcia, Alessandro; Gaidolfi, Elena; Bruselles, Alessandro; Mancini, Cecilia; Cavalieri, Simona; Molinatto, Cristina; Cirillo Silengo, Margherita; Ferrero, Giovanni Battista; Tartaglia, Marco; Brusco, Alfredo
2016-07-01
Whole exome sequencing (WES) is a powerful tool to identify clinically undefined forms of intellectual disability/developmental delay (ID/DD), especially in consanguineous families. Here we report the genetic definition of two sporadic cases, with syndromic ID/DD for whom array-Comparative Genomic Hybridization (aCGH) identified a de novo copy number variant (CNV) of uncertain significance. The phenotypes included microcephaly with brachycephaly and a distinctive facies in one proband, and hypotonia in the legs and mild ataxia in the other. WES allowed identification of a functionally relevant homozygous variant affecting a known disease gene for rare syndromic ID/DD in each proband, that is, c.1423C>T (p.Arg377*) in the Trafficking Protein Particle Complex 9 (TRAPPC9), and c.154T>C (p.Cys52Arg) in the Very Low Density Lipoprotein Receptor (VLDLR). Four mutations affecting TRAPPC9 have been previously reported, and the present finding further depicts this syndromic form of ID, which includes microcephaly with brachycephaly, corpus callosum hypoplasia, facial dysmorphism, and overweight. VLDLR-associated cerebellar hypoplasia (VLDLR-CH) is characterized by non-progressive congenital ataxia and moderate-to-profound intellectual disability. The c.154T>C (p.Cys52Arg) mutation was associated with a very mild form of ataxia, mild intellectual disability, and cerebellar hypoplasia without cortical gyri simplification. In conclusion, we report two novel cases with rare causes of autosomal recessive ID, which document how interpreting de novo array-CGH variants represents a challenge in consanguineous families; as such, clinical WES should be considered in diagnostic testing. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Pritchard, Colin C; Salipante, Stephen J; Koehler, Karen; Smith, Christina; Scroggins, Sheena; Wood, Brent; Wu, David; Lee, Ming K; Dintzis, Suzanne; Adey, Andrew; Liu, Yajuan; Eaton, Keith D; Martins, Renato; Stricker, Kari; Margolin, Kim A; Hoffman, Noah; Churpek, Jane E; Tait, Jonathan F; King, Mary-Claire; Walsh, Tom
2014-01-01
Recent years have seen development and implementation of anticancer therapies targeted to particular gene mutations, but methods to assay clinical cancer specimens in a comprehensive way for the critical mutations remain underdeveloped. We have developed UW-OncoPlex, a clinical molecular diagnostic assay to provide simultaneous deep-sequencing information, based on >500× average coverage, for all classes of mutations in 194 clinically relevant genes. To validate UW-OncoPlex, we tested 98 previously characterized clinical tumor specimens from 10 different cancer types, including 41 formalin-fixed paraffin-embedded tissue samples. Mixing studies indicated reliable mutation detection in samples with ≥ 10% tumor cells. In clinical samples with ≥ 10% tumor cells, UW-OncoPlex correctly identified 129 of 130 known mutations [sensitivity 99.2%, (95% CI, 95.8%-99.9%)], including single nucleotide variants, small insertions and deletions, internal tandem duplications, gene copy number gains and amplifications, gene copy losses, chromosomal gains and losses, and actionable genomic rearrangements, including ALK-EML4, ROS1, PML-RARA, and BCR-ABL. In the same samples, the assay also identified actionable point mutations in genes not previously analyzed and novel gene rearrangements of MLL and GRIK4 in melanoma, and of ASXL1, PIK3R1, and SGCZ in acute myeloid leukemia. To best guide existing and emerging treatment regimens and facilitate integration of genomic testing with patient care, we developed a framework for data analysis, decision support, and reporting clinically actionable results. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.
Vlad, Marcel Ovidiu; Schönfisch, Birgitt; Mackey, Michael C.
1996-02-01
The possible occurrence of ergodic behavior for large times is investigated in the case of stationary random processes with memory. It is shown that for finite times the time average of a state function is generally a random variable and thus two types of cumulants can be introduced: for the time average and for the statistical ensemble, respectively. In the limit of infinite time a transition from the random to the deterministic behavior of the time average may occur, resulting in an ergodic behavior. The conditions of occurrence of this transition are investigated by analyzing the scaling behavior of the cumulants of the time average. A general approach for the computation of these cumulants is developed; explicit computations are presented both for short and long memory in the particular case of separable stationary processes for which the cumulants of a statistical ensemble can be factorized into products of functions depending on binary time differences. In both cases the ergodic behavior emerges for large times provided that the cumulants of a statistical ensemble decrease to zero as the time differences increase to infinity. The analysis leads to the surprising conclusion that the scaling behavior of the cumulants of the time average is relatively insensitive to the type of memory considered: both for short and long memory the cumulants of the time average obey inverse different from zero for large time differences, then the time averaage is random even as the length of the total time interval tends to infinity and the ergodic behavior no longer holds. The theory is applied to the study of long range correlations of nucleotide sequences in DNA; in this case the length t of a sequence of nucleotides plays the role of the time variable. A proportionality relationship is established between the cumulants of the pyrimidine excess in a sequence of length t and the cumulants of the time (length) average of the probability of occurrence of a pyrimidine. It is shown
Berwouts, Dieter; De Wolf, Katrien; Lambert, Bieke; Bultijnck, Renée; De Neve, Wilfried; De Lobel, Lizzy; Jans, Lennart; Goetghebeur, Els; Speleers, Bruno; Olteanu, Luiza A M; Madani, Indira; Goethals, Ingeborg; Ost, Piet
2015-05-01
Antalgic radiotherapy for bone metastases might be improved by implementing biological information in the radiotherapy planning using (18)F-FDG-PET-CT based dose painting by numbers (DPBN). Patients with uncomplicated painful bone metastases were randomized (1:1:1) and blinded to receive either 8Gy in a single fraction with conventionally planned radiotherapy (arm A) or 8Gy in a single fraction with DPBN (dose range between 610Gy and 10Gy) (arm B) or 16Gy in a single fraction with DPBN (dose range between 1410Gy and 18Gy) (arm C). The primary endpoint was overall pain response at 1month. The phase II trial was designed to select the experimental arm with sufficient promise of efficacy to continue to a phase III trial. Forty-five patients were randomized. Eight (53%), 12 (80%) and 9 patients (60%) had an overall response to treatment in arm A, B and C, respectively. The estimated odds ratio of overall response for arm B vs. A is 3.5 (95% CI: 0.44-17.71, p=0.12). The estimated odds ratio of arm C vs. A is 1.31 (95% CI: 0.31-5.58, p=0.71). A single fraction of 8Gy with DPBN will be further evaluated in a phase III-trial. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Jung, Dong-Hyuk; Lee, Yong-Jae; Kim, Chun-Bae; Kim, Jang-Young; Shin, Seung-Hun; Park, Jong-Ku
2016-02-01
It has been observed that mitochondrial dysfunction is associated with an increased risk of metabolic syndrome. There is growing evidence that hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis and hormone (testosterone and growth hormone) deficiency may lead to metabolic syndrome. Recent studies have reported that ginseng treatment improves mitochondrial and HPA-axis function and increases anabolic hormone secretion. The objective of this study was to investigate the effect of red ginseng (RG) on metabolic syndrome, hormones, and mitochondrial function using leukocyte mitochondrial DNA copy number in men with metabolic syndrome. We performed a randomized, double-blind, placebo-controlled study in 62 subjects who were not taking drugs that could affect their metabolic function. A total of 62 men with metabolic syndrome were randomly assigned to either an RG group (3.0g/day) or a placebo group for 4 weeks. We analyzed changes in metabolic syndrome components, leukocyte mitochondrial DNA copy number, hormones (total testosterone, IGF-1, cortisol, and DHEAS) and inflammatory markers (C-reactive protein, ferritin) from baseline to 4 weeks. Significant improvement in mitochondrial function (95% CI -44.9 to -1.3) and an increase in total testosterone (95% CI -70.1 to -1.0) and IGF-1(P=0.01) levels were observed in the RG group when compared with the placebo group. Diastolic blood pressure (95% CI 2.0-9.4) and serum cortisol (95% CI 1.1-5.5) significantly decreased in the RG group. We found evidence that RG had a favorable effect on mitochondrial function and hormones in men with metabolic syndrome. Copyright © 2015 Elsevier Ltd. All rights reserved.
National Research Council Canada - National Science Library
Do, Hongdo; Dobrovic, Alexander
2009-01-01
.... High resolution melting (HRM) is more sensitive than sequencing but identification of the mutation is desirable, particularly when it is important to discriminate false positives due to PCR errors or template degradation from true...
Directory of Open Access Journals (Sweden)
Simon A McManus
Full Text Available The process of in vitro selection has led to the discovery of many aptamers with potential to be developed into inhibitors and biosensors, but problems in isolating aptamers against certain targets with desired affinity and specificity still remain. One possible improvement is to use libraries enhanced for motifs repeatedly isolated in aptamer molecules. One such frequently observed motif is the two-tiered guanine quadruplex. In this study we investigated whether DNA libraries could be designed to contain a large fraction of molecules capable of folding into two-tiered guanine quadruplexes. Using comprehensive circular dichroism analysis, we found that DNA libraries could be designed to contain a large proportion of sequences that adopt guanine quadruplex structures. Analysis of individual sequences from a small library revealed a mixture of quadruplexes of different topologies providing the diversity desired for an in vitro selection. We also found that primer-binding sites are detrimental to quadruplex formation and devised a method for post-selection amplification of primer-less quadruplex libraries. With the development of guanine quadruplex enriched DNA libraries, it should be possible to improve the chances of isolating aptamers that utilize a quadruplex scaffold and enhance the success of in vitro selection experiments.
Autocorrelation peaks in congruential pseudorandom number generators
Neuman, F.; Merrick, R. B.
1976-01-01
The complete correlation structure of several congruential pseudorandom number generators (PRNG) of the same type and small cycle length was studied to deal with the problem of congruential PRNG almost repeating themselves at intervals smaller than their cycle lengths, during simulation of bandpass filtered normal random noise. Maximum period multiplicative and mixed congruential generators were studied, with inferences drawn from examination of several tractable members of a class of random number generators, and moduli from 2 to the 5th power to 2 to the 9th power. High correlation is shown to exist in mixed and multiplicative congruential random number generators and prime moduli Lehmer generators for shifts a fraction of their cycle length. The random noise sequences in question are required when simulating electrical noise, air turbulence, or time variation of wind parameters.
Dei Cas, Alessandra; Spigoni, Valentina; Cito, Monia; Aldigeri, Raffaella; Ridolfi, Valentina; Marchesi, Elisabetta; Marina, Michela; Derlindati, Eleonora; Aloe, Rosalia; Bonadonna, Riccardo C; Zavaroni, Ivana
2017-02-23
Fewer circulating endothelial progenitor cells (EPCs) and increased plasma (C-term) stromal cell-derived factor 1α (SDF-1α), a substrate of DPP-4, are biomarkers, and perhaps mediators, of cardiovascular risk and mortality. Short-term/acute treatment with DPP-4 inhibitors improve EPC bioavailability; however, long-term effects of DPP-4i on EPCs bioavailability/plasma (C-term) SDF-1α are unknown. Randomized (2:1) open-label trial to compare the effects of vildagliptin (V) (100 mg/day) vs glibenclamide (G) (2.5 mg bid to a maximal dose of 5 mg bid) on circulating EPC levels at 4 and 12 months of treatment in 64 patients with type 2 diabetes in metformin failure. At baseline, and after 4 and 12 months, main clinical/biohumoral parameters, inflammatory biomarkers, concomitant therapies, EPC number (CD34+/CD133+/KDR+/106 cytometric events) and plasma (C-term) SDF-1α (R&D system) were assessed. Baseline characteristics were comparable in the two groups. V and G similarly and significantly (p < 0.0001) improved glucose control. At 12 months, V significantly increased EPC number (p < 0.05) and significantly reduced (C-term) SDF-1α plasma levels (p < 0.01) compared to G, with no differences in inflammatory biomarkers. V exerts a long-term favorable effect on EPC and (C-term) SDF-1α levels at glucose equipoise, thereby implying a putative beneficial effect on vascular integrity. Trial registration Clinical Trials number: NCT01822548; name: Effect of Vildagliptin vs. Glibenclamide on Circulating Endothelial Progenitor Cell Number Type 2 Diabetes. Registered 28 March, 2013.
Yu, Zhenhua; Li, Ao; Wang, Minghui
2017-03-15
Copy number alterations (CNA) and loss of heterozygosity (LOH) represent a large proportion of genetic structural variations of cancer genomes. These aberrations are continuously accumulated during the procedure of clonal evolution and patterned by phylogenetic branching. This invariably results in the emergence of multiple cell populations with distinct complement of mutational landscapes in tumor sample. With the advent of next-generation sequencing technology, inference of subclonal populations has become one of the focused interests in cancer-associated studies, and is usually based on the assessment of combinations of somatic single-nucleotide variations (SNV), CNA and LOH. However, cancer samples often have several inherent issues, such as contamination of normal stroma, tumor aneuploidy and intra-tumor heterogeneity. Addressing these critical issues is imperative for accurate profiling of clonal architecture. We present CLImAT-HET, a computational method designed for capturing clonal diversity in the CNA/LOH dimensions by taking into account the intra-tumor heterogeneity issue, in the case where a reference or matched normal sample is absent. The algorithm quantitatively represents the clonal identification problem using a factorial hidden Markov model, and takes an integrated analysis of read counts and allele frequency data. It is able to infer subclonal CNA and LOH events as well as the fraction of cells harboring each event. The results on simulated datasets indicate that CLImAT-HET has high power to identify CNA/LOH segments, it achieves an average accuracy of 0.87. It can also accurately infer proportion of each clonal population with an overall Pearson correlation coefficient of 0.99 and a mean absolute error of 0.02. CLImAT-HET shows significant advantages when compared with other existing methods. Application of CLImAT-HET to 5 primary triple negative breast cancer samples demonstrates its ability to capture clonal diversity in the CAN
Energy Technology Data Exchange (ETDEWEB)
Qi, Shuyan [Department of Chemical Engineering, Department of Chemistry, and Materials Science Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720 (United States); Chakraborty, Arup K. [Department of Chemical Engineering, Department of Chemistry, and Materials Science Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720 (United States)
2000-01-15
We use a Landau theory to study the instability of the homogeneous state of a mixture of linear random copolymers and diblock copolymers. Interesting features of the calculated structure factors for different components of the mixture are found, which can be directly compared with scattering experiments with selectively deuterated samples. We also investigate the least stable concentration fluctuations and find four different types of segregation modes at the spinodal depending upon the characteristics of the mixture (e.g., average compositions, statistical correlation lengths and volume fractions). The different segregation modes are also indicative of the kinetic pathways leading to the formation of ordered microstructures. Experiments probing these pathways are suggested. (c) 2000 American Institute of Physics.
A large-scale study of the random variability of a coding sequence: a study on the CFTR gene.
Modiano, Guido; Bombieri, Cristina; Ciminelli, Bianca Maria; Belpinati, Francesca; Giorgi, Silvia; Georges, Marie des; Scotet, Virginie; Pompei, Fiorenza; Ciccacci, Cinzia; Guittard, Caroline; Audrézet, Marie Pierre; Begnini, Angela; Toepfer, Michael; Macek, Milan; Ferec, Claude; Claustres, Mireille; Pignatti, Pier Franco
2005-02-01
Coding single nucleotide substitutions (cSNSs) have been studied on hundreds of genes using small samples (n(g) approximately 100-150 genes). In the present investigation, a large random European population sample (average n(g) approximately 1500) was studied for a single gene, the CFTR (Cystic Fibrosis Transmembrane conductance Regulator). The nonsynonymous (NS) substitutions exhibited, in accordance with previous reports, a mean probability of being polymorphic (q > 0.005), much lower than that of the synonymous (S) substitutions, but they showed a similar rate of subpolymorphic (q < 0.005) variability. This indicates that, in autosomal genes that may have harmful recessive alleles (nonduplicated genes with important functions), genetic drift overwhelms selection in the subpolymorphic range of variability, making disadvantageous alleles behave as neutral. These results imply that the majority of the subpolymorphic nonsynonymous alleles of these genes are selectively negative or even pathogenic.
Armstrong, Kathleen A; Coyte, Peter C; Brown, Mitchell; Beber, Brett; Semple, John L
2017-07-01
In the age of information and patient-centered care, new methods of delivering postoperative care must be developed and evaluated. To determine whether follow-up care delivered via a mobile app can be used to avert in-person follow-up care visits compared with conventional, in-person follow-up care in the first 30 days following ambulatory surgery. A randomized clinical trial was conducted from February 1 to August 31, 2015, among ambulatory patients undergoing breast reconstruction at an academic ambulatory care hospital. Patients were randomly assigned to receive follow-up care via a mobile app or at an in-person visit during the first 30 days after the operation. Analysis was intention-to-treat. The primary end point was the number of in-person follow-up visits during the first 30 days after the operation. Secondary end points were the number of telephone calls and emails to health care professionals, patient-reported convenience and satisfaction scores, and rates of complications. Of the 65 women in the study (mean [SD] age, 47.7 [13.4] years), 32 (49%) were in the mobile app group, and 33 (51%) were in the in-person follow-up care group. Those in the mobile app group attended a mean of 0.66 in-person visits, vs 1.64 in-person visits in the in-person follow-up care group, for a difference of 0.40 times fewer in-person visits (95% CI, 0.24-0.66; P mobile app group reported higher convenience scores than the in-person follow-up care group (incidence rate ratio, 1.39; 95% CI, 1.09-1.77; P = .008). There was no difference between groups in the number of telephone communications, satisfaction scores, or complication rates. Patients undergoing ambulatory breast reconstruction can use follow-up care via a mobile app to avert in-person follow-up visits during the first 30 days after the operation. Mobile app follow-up care affects neither complication rates nor patient-reported satisfaction scores, but it improves patient-reported convenience scores
Short sequence motifs, overrepresented in mammalian conservednon-coding sequences
Energy Technology Data Exchange (ETDEWEB)
Minovitsky, Simon; Stegmaier, Philip; Kel, Alexander; Kondrashov,Alexey S.; Dubchak, Inna
2007-02-21
Background: A substantial fraction of non-coding DNAsequences of multicellular eukaryotes is under selective constraint. Inparticular, ~;5 percent of the human genome consists of conservednon-coding sequences (CNSs). CNSs differ from other genomic sequences intheir nucleotide composition and must play important functional roles,which mostly remain obscure.Results: We investigated relative abundancesof short sequence motifs in all human CNSs present in the human/mousewhole-genome alignments vs. three background sets of sequences: (i)weakly conserved or unconserved non-coding sequences (non-CNSs); (ii)near-promoter sequences (located between nucleotides -500 and -1500,relative to a start of transcription); and (iii) random sequences withthe same nucleotide composition as that of CNSs. When compared tonon-CNSs and near-promoter sequences, CNSs possess an excess of AT-richmotifs, often containing runs of identical nucleotides. In contrast, whencompared to random sequences, CNSs contain an excess of GC-rich motifswhich, however, lack CpG dinucleotides. Thus, abundance of short sequencemotifs in human CNSs, taken as a whole, is mostly determined by theiroverall compositional properties and not by overrepresentation of anyspecific short motifs. These properties are: (i) high AT-content of CNSs,(ii) a tendency, probably due to context-dependent mutation, of A's andT's to clump, (iii) presence of short GC-rich regions, and (iv) avoidanceof CpG contexts, due to their hypermutability. Only a small number ofshort motifs, overrepresented in all human CNSs are similar to bindingsites of transcription factors from the FOX family.Conclusion: Human CNSsas a whole appear to be too broad a class of sequences to possess strongfootprints of any short sequence-specific functions. Such footprintsshould be studied at the level of functional subclasses of CNSs, such asthose which flank genes with a particular pattern of expression. Overallproperties of CNSs are affected by
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Fatih Mehmet Tok
2016-09-01
Full Text Available The genetic diversity and pathogenicity/virulence among 60 eggplant Sclerotinia sclerotiorum isolates collected from six different geographic regions of Turkey were analysed using mycelial compatibility groupings (MCGs, random amplified polymorphic DNA (RAPD and simple sequence repeat (SSR polymorphism. By MCG tests, the isolates were classified into 22 groups. Out of 22 MCGs, 36% were represented each by a single isolate. The isolates showed great variability for virulence regardless of MCG and geographic origin. Based on the results of RAPD and SSR analyses, 60 S. sclerotiorum isolates representing 22 MCGs were grouped in 2 and 3 distinct clusters, respectively. Analyses using RAPD and SSR markers illustrated that cluster groupings or genetic distance of S. sclerotiorum populations from eggplant were not distinctly relative to the MCG, geographical origin and virulence diversity. The patterns obtained revealed a high heterogeneity of genetic composition and suggested the occurrence of clonal and sexual reproduction of S. sclerotiorum on eggplant in the areas surveyed.
Baum, Leonard E.
2017-01-01
We suggest other models of sieve generated sequences like the Sieve of Eratosthenes to explain randomness properties of the prime numbers, like the twin prime conjecture, the lim sup conjecture, the Riemann conjecture, and the prime number theorem.
DEFF Research Database (Denmark)
Scheibye-Alsing, Karsten; Hoffmann, S.; Frankel, Annett Maria
2009-01-01
Despite the rapidly increasing number of sequenced and re-sequenced genomes, many issues regarding the computational assembly of large-scale sequencing data have remain unresolved. Computational assembly is crucial in large genome projects as well for the evolving high-throughput technologies...... and plays an important role in processing the information generated by these methods. Here, we provide a comprehensive overview of the current publicly available sequence assembly programs. We describe the basic principles of computational assembly along with the main concerns, such as repetitive sequences...... in genomic DNA, highly expressed genes and alternative transcripts in EST sequences. We summarize existing comparisons of different assemblers and provide a detailed descriptions and directions for download of assembly programs at: http://genome.ku.dk/resources/assembly/methods.html....
Bayerl, Helmut; Kraus, Robert H S; Nowak, Carsten; Foerster, Daniel W; Fickel, Joerns; Kuehn, Ralph
2017-09-15
Biodiversity has suffered a dramatic global decline during the past decades, and monitoring tools are urgently needed providing data for the development and evaluation of conservation efforts both on a species and on a genetic level. However, in wild species, the assessment of genetic diversity is often hampered by the lack of suitable genetic markers. In this article, we present Random Amplicon Sequencing (RAMseq), a novel approach for fast and cost-effective detection of single nucleotide polymorphisms (SNPs) in nonmodel species by semideep sequencing of random amplicons. By applying RAMseq to the Eurasian otter (Lutra lutra), we identified 238 putative SNPs after quality filtering of all candidate loci and were able to validate 32 of 77 loci tested. In a second step, we evaluated the genotyping performance of these SNP loci in noninvasive samples, one of the most challenging genotyping applications, by comparing it with genotyping results of the same faecal samples at microsatellite markers. We compared (i) polymerase chain reaction (PCR) success rate, (ii) genotyping errors and (iii) Mendelian inheritance (population parameters). SNPs produced a significantly higher PCR success rate (75.5% vs. 65.1%) and lower mean allelic error rate (8.8% vs. 13.3%) than microsatellites, but showed a higher allelic dropout rate (29.7% vs. 19.8%). Genotyping results showed no deviations from Mendelian inheritance in any of the SNP loci. Hence, RAMseq appears to be a valuable tool for the detection of genetic markers in nonmodel species, which is a common challenge in conservation genetic studies. © 2017 John Wiley & Sons Ltd.
Pakarainen, Tomi; Raitanen, Jani; Talala, Kirsi; Taari, Kimmo; Kujala, Paula; Tammela, Teuvo L; Auvinen, Anssi
2016-09-01
The multicenter European Randomized Study of Screening for Prostate Cancer has shown a 21% reduction in prostate cancer (PC) mortality by prostate-specific antigen-based screening, with substantial overdiagnosis. In the present study, we analyzed the incidence of PC after screening in relation to the number of screening rounds attended in the Finnish section of the trial. To evaluate the possible reduction in PC incidence following completed screening cycles in relation to the number of screening rounds attended. The participants in the screening arm of the Finnish screening trial (29 298 men) were divided into subgroups of men who had participated at one, two, or three screening rounds. A reference group was formed of the 43 151 men in the control arm by selecting age-matched controls for each subgroup of the screening participants. PC cases diagnosed after screening were identified from the Finnish Cancer Registry until the end of 2011. Follow-up of the screened men started 12 mo (365 d) after the last screening attendance and a similar date was assigned to the men in the control arm. A total of 1514 new PCs cases (cumulative incidence 5.2%) were diagnosed among the screened men after the last screening attendance. In the reference group formed from the control arm, 2683 cases (6.2%) occurred. The hazard ratio (HR) for PC among nonparticipants in the screening arm was 0.89 (95% confidence interval [CI] 0.79-0.99) compared with their controls. Among participants, the HR in those who participated once was 1.39 (95% CI 1.22-1.57), among men who participated twice the HR was 0.97 (95% CI 0.86-1.10), and among men screened three times the HR was 0.57 (95% CI 0.49-0.68). A limitation of the study was that the comparison by attendance is not based on randomization. The postscreening PC incidence is reduced after attending three screening rounds, but not after only one or two rounds. Thus, the increased cancer detection at screening is compensated by a subsequent risk
Jang, Jae-Won; Seo, Ji-Hyung; Jo, Min-Ho; Lee, Young-Joo; Cho, Young-Wuk; Yim, Sung-Vin; Lee, Kyung-Tae
2013-02-01
Levodropropizine is an oral non-opioid anti-tussive drug used in treatment of cough. A new generic 60 mg capsule formulation of levodropropizine has recently been developed. The aim of this study was to assess the pharmacokinetics and bioequivalence of the test (capsule) formulation and reference (syrup) formulation of levodropropizine (60 mg) in healthy, fasted, male Korean volunteers. This was a single-dose, randomized sequence, open-label, 2-period crossover study conducted in healthy male Korean volunteers in the fasted state at Kyung Hee University Medical Center (Seoul, Republic of Korea). A single oral dose of the test or reference formulation was followed by a 1-week washout period, after which subjects received the alternative formulation. Blood samples were collected at 0 (predose), 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after study drug administration. Plasma concentration of levodropropizine was determined using a validated liquid chromatography tandem mass spectrometry (LCMS/ MS) method. The formulations were considered bioequivalent if the 90% CIs for C(max), AUC(0-12h) and AUC(0-∞) were within the predetermined bioequivalence range (80 - 125%, according to the guidelines of the Korea Food and Drug Administration (Korea FDA)). Tolerability was evaluated throughout the study based on vital sign measurements, laboratory analysis (blood biochemistry, hematology, hepatic function and urinalysis) and subject interviews concerning adverse events (AEs). A total of 36 male Korean subjects (mean (SD) age, 23.9 (2.4) years (range 19 - 30 years); height, 176.2 (6.1) cm (range 161 - 190 cm); weight, 69.8 (9.1) kg (range 54.0 - 92.2 kg); body mass index, 22.4 (2.1) kg/m2 (range 19.1 - 28.3 kg/m2)) was enrolled and completed the study. The mean values for C(max), t(max), AUC(0-12h), and AUC(0-∞) with the test formulation of levodropropizine were 331.51 ng/ml, 0.60 hours, 784.32 ng×h/ml, and 825.82 ng×h/ml, respectively; for the reference
Metaheuristic approaches to order sequencing on a unidirectional ...
African Journals Online (AJOL)
In this paper the sequencing of orders on a unidirectional picking line is considered. The aim of the order sequencing is to minimise the number of cycles travelled by a picker within the picking line to complete all orders. A tabu search, simulated annealing, genetic algorithm, generalised extremal optimisation and a random ...
Armstrong, Kathleen A; Coyte, Peter C; Bhatia, R Sacha; Semple, John L
2015-06-03
Women's College Hospital, Toronto, Canada, offers specialized ambulatory surgical procedures. Patients often travel great distances to undergo surgery. Most patients receiving ambulatory surgery have a low rate of postoperative events necessitating clinic visits. However, regular follow-up is still considered important in the early postoperative phase. Increasingly, telemedicine is used to overcome the distance patients must travel to receive specialized care. Telemedicine data suggest that mobile monitoring and follow-up care is valued by patients and can reduce costs to society. Women's College Hospital has used a mobile app (QoC Health Inc) to complement in-person postoperative follow-up care for breast reconstruction patients. Preliminary studies suggest that mobile app follow-up care is feasible, can avert in-person follow-up care, and is cost-effective from a societal and health care system perspective. We hope to expand the use of mobile app follow-up care through its formal assessment in a randomized controlled trial. In postoperative ambulatory surgery patients at Women's College Hospital (WCH), can we avert in-person follow-up care through the use of mobile app follow-up care compared to conventional, in-person follow-up care in the first 30 days after surgery. This will be a pragmatic, single-center, open, controlled, 2-arm parallel-group superiority randomized trial comparing mobile app and in-person follow-up care over the first month following surgery. The patient population will comprise all postoperative ambulatory surgery patients at WCH undergoing breast reconstruction. The intervention consists of a postoperative mobile app follow-up care using the quality of recovery-9 (QoR9) and a pain visual analog scale (VAS), surgery-specific questions, and surgical site photos submitted daily for the first 2 weeks and weekly for the following 2 weeks. The primary outcome is the total number of physician visits related to the surgery over the first 30-days
Friederichs, Hendrik; Ligges, Sandra; Weissenstein, Anne
2014-02-01
Physicians and medical students may lack sufficient numeracy skills to make treatment decisions, interpret test results, and practice evidence-based medicine. We evaluated whether the use of a tree diagram without numerical values as an aid for numerical processing might improve students' test results when dealing with percentages. A prospective randomized study was carried out with 102 third-year students. Participants received 3 diagnostic test problems and were asked to determine positive predictive values. The information in these tests was expressed either in (1) natural frequencies, (2) conditional probabilities, or (3) conditional probabilities with a tree diagram without numbers. Ninety-eight (96.1%) complete data sets could be obtained. The group working with natural frequencies achieved significantly higher test results (n = 29, mean score: 1.1, P = 0.045) than the group working with conditional probabilities (n = 34, mean score: 0.56). The students who were given a tree diagram in addition to conditional probabilities (n = 35, mean score: 1.26) also achieved significantly better scores than the group with conditional probabilities alone (P = 0.008). The difference between the group who had received natural frequencies and the group working with conditional probabilities and the tree diagram was not significant. We suggest the use of a tree diagram as a visual aid when dealing with diagnostic tests expressed in conditional probabilities.
Apanasovich, Tatiyana V.
2012-03-01
We introduce a valid parametric family of cross-covariance functions for multivariate spatial random fields where each component has a covariance function from a well-celebrated Matérn class. Unlike previous attempts, our model indeed allows for various smoothnesses and rates of correlation decay for any number of vector components.We present the conditions on the parameter space that result in valid models with varying degrees of complexity. We discuss practical implementations, including reparameterizations to reflect the conditions on the parameter space and an iterative algorithm to increase the computational efficiency. We perform various Monte Carlo simulation experiments to explore the performances of our approach in terms of estimation and cokriging. The application of the proposed multivariate Matérnmodel is illustrated on two meteorological datasets: temperature/pressure over the Pacific Northwest (bivariate) and wind/temperature/pressure in Oklahoma (trivariate). In the latter case, our flexible trivariate Matérn model is valid and yields better predictive scores compared with a parsimonious model with common scale parameters. © 2012 American Statistical Association.
Directory of Open Access Journals (Sweden)
TANET Antoine
2016-09-01
Full Text Available Introduction: Individuals with Autism Spectrum Disorder (ASD who also exhibit severe to moderate ranges of intellectual disability (ID still face many challenges (i.e. less evidence-based trials, less inclusion in school with peers.Methods: We implemented a novel model called the Developmental and Sequenced One-to-One Educational Intervention (DS1-EI in 5-9-year-old children with co-occurring ASD and ID. The treatment protocol was adapted for school implementation by designing it using an educational agenda. The intervention was based on intensity, regular assessments, updating objectives, encouraging spontaneous communication, promoting skills through play with peers, supporting positive behaviours, providing supervision, capitalizing on teachers’ unique skills, and providing developmental and sequenced learning. Developmental learning implies that the focus of training is what is close to the developmental expectations given a child’s development in a specific domain. Sequenced learning means that the teacher changes the learning activities every 10-15 minutes to maintain the child’s attention in the context of an anticipated time agenda.We selected 11 French institutions in which we implemented the model in small classrooms. Each institution recruited participants per dyads matched by age, sex and developmental quotient. Patients from each dyad were then randomized to a DS1-EI group or a Treatment as usual (TAU group for 36 months. The primary variables – the Childhood Autism Rating scale (CARS and the psychoeducational profile (PEP-3 – will be blindly assessed by independent raters at the 18-month and 36-month follow-up.Discussion and baseline description: We enrolled 75 participants: 38 were randomized to the DS1-EI and 37 to the TAU groups. At enrolment, we found no significant differences in participants’ characteristics between groups. As expected, exposure to school was the only significant difference (9.4 (±4.1 h/week in
Pritchard, Colin C.; Salipante, Stephen J.; Koehler, Karen; Smith, Christina; Scroggins, Sheena; Wood, Brent; Wu, David; Lee, Ming K.; Dintzis, Suzanne; Adey, Andrew; Liu, Yajuan; Keith D Eaton; Martins, Renato; Stricker, Kari; Margolin, Kim A
2014-01-01
Recent years have seen development and implementation of anticancer therapies targeted to particular gene mutations, but methods to assay clinical cancer specimens in a comprehensive way for the critical mutations remain underdeveloped. We have developed UW-OncoPlex, a clinical molecular diagnostic assay to provide simultaneous deep-sequencing information, based on >500× average coverage, for all classes of mutations in 194 clinically relevant genes. To validate UW-OncoPlex, we tested 98 prev...
Hou, Qingzhen; De Geest, Paul F.G.; Vranken, Wim F.; Heringa, Jaap; Feenstra, K. Anton
2017-01-01
Motivation: Genome sequencing is producing an ever-increasing amount of associated protein sequences. Few of these sequences have experimentally validated annotations, however, and computational predictions are becoming increasingly successful in producing such annotations. One key challenge remains
Blocked Randomization with Randomly Selected Block Sizes
Directory of Open Access Journals (Sweden)
Jimmy Efird
2010-12-01
Full Text Available When planning a randomized clinical trial, careful consideration must be given to how participants are selected for various arms of a study. Selection and accidental bias may occur when participants are not assigned to study groups with equal probability. A simple random allocation scheme is a process by which each participant has equal likelihood of being assigned to treatment versus referent groups. However, by chance an unequal number of individuals may be assigned to each arm of the study and thus decrease the power to detect statistically significant differences between groups. Block randomization is a commonly used technique in clinical trial design to reduce bias and achieve balance in the allocation of participants to treatment arms, especially when the sample size is small. This method increases the probability that each arm will contain an equal number of individuals by sequencing participant assignments by block. Yet still, the allocation process may be predictable, for example, when the investigator is not blind and the block size is fixed. This paper provides an overview of blocked randomization and illustrates how to avoid selection bias by using random block sizes.
Blocked randomization with randomly selected block sizes.
Efird, Jimmy
2011-01-01
When planning a randomized clinical trial, careful consideration must be given to how participants are selected for various arms of a study. Selection and accidental bias may occur when participants are not assigned to study groups with equal probability. A simple random allocation scheme is a process by which each participant has equal likelihood of being assigned to treatment versus referent groups. However, by chance an unequal number of individuals may be assigned to each arm of the study and thus decrease the power to detect statistically significant differences between groups. Block randomization is a commonly used technique in clinical trial design to reduce bias and achieve balance in the allocation of participants to treatment arms, especially when the sample size is small. This method increases the probability that each arm will contain an equal number of individuals by sequencing participant assignments by block. Yet still, the allocation process may be predictable, for example, when the investigator is not blind and the block size is fixed. This paper provides an overview of blocked randomization and illustrates how to avoid selection bias by using random block sizes.
Yokota, Shin-ichi; Konno, Mutsuko; Fujiwara, Shin-ichi; Toita, Nariaki; Takahashi, Michiko; Yamamoto, Soh; Ogasawara, Noriko; Shiraishi, Tsukasa
2015-10-01
The infection route of Helicobacter pylori has been recognized to be mainly intrafamilial, preferentially mother-to-child, especially in developed countries. To determine the transmission route, we examined whether multilocus sequence typing (MLST) was useful for analysis of intrafamilial infection. The possibility of intraspousal infection was also evaluated. Clonal relationships between strains derived from 35 index Japanese pediatric patients, and their family members were analyzed by two genetic typing procedures, MLST and random amplified polymorphic DNA (RAPD) fingerprinting. Mostly coincident results were obtained by MLST and RAPD. By MLST, the allele of loci in the isolates mostly matched between the index child and both the father and mother for 9 (25.7%) of the 35 patients, between the index child and the mother for 25 (60.0%) of the 35 patients. MLST is useful for analyzing the infection route of H. pylori as a highly reproducible method. Intrafamilial, especially mother-to-children and sibling, infection is the dominant transmission route. Intraspousal infection is also thought to occur in about a quarter in the Japanese families. © 2015 John Wiley & Sons Ltd.
Harrop, Thomas W R; Sztal, Tamar; Lumb, Christopher; Good, Robert T; Daborn, Phillip J; Batterham, Philip; Chung, Henry
2014-01-01
Widespread use of insecticides has led to insecticide resistance in many populations of insects. In some populations, resistance has evolved to multiple pesticides. In Drosophila melanogaster, resistance to multiple classes of insecticide is due to the overexpression of a single cytochrome P450 gene, Cyp6g1. Overexpression of Cyp6g1 appears to have evolved in parallel in Drosophila simulans, a sibling species of D. melanogaster, where it is also associated with insecticide resistance. However, it is not known whether the ability of the CYP6G1 enzyme to provide resistance to multiple insecticides evolved recently in D. melanogaster or if this function is present in all Drosophila species. Here we show that duplication of the Cyp6g1 gene occurred at least four times during the evolution of different Drosophila species, and the ability of CYP6G1 to confer resistance to multiple insecticides exists in D. melanogaster and D. simulans but not in Drosophila willistoni or Drosophila virilis. In D. virilis, which has multiple copies of Cyp6g1, one copy confers resistance to DDT and another to nitenpyram, suggesting that the divergence of protein sequence between copies subsequent to the duplication affected the activity of the enzyme. All orthologs tested conferred resistance to one or more insecticides, suggesting that CYP6G1 had the capacity to provide resistance to anthropogenic chemicals before they existed. Finally, we show that expression of Cyp6g1 in the Malpighian tubules, which contributes to DDT resistance in D. melanogaster, is specific to the D. melanogaster-D. simulans lineage. Our results suggest that a combination of gene duplication, regulatory changes and protein coding changes has taken place at the Cyp6g1 locus during evolution and this locus may play a role in providing resistance to different environmental toxins in different Drosophila species.
Directory of Open Access Journals (Sweden)
Thomas W R Harrop
Full Text Available Widespread use of insecticides has led to insecticide resistance in many populations of insects. In some populations, resistance has evolved to multiple pesticides. In Drosophila melanogaster, resistance to multiple classes of insecticide is due to the overexpression of a single cytochrome P450 gene, Cyp6g1. Overexpression of Cyp6g1 appears to have evolved in parallel in Drosophila simulans, a sibling species of D. melanogaster, where it is also associated with insecticide resistance. However, it is not known whether the ability of the CYP6G1 enzyme to provide resistance to multiple insecticides evolved recently in D. melanogaster or if this function is present in all Drosophila species. Here we show that duplication of the Cyp6g1 gene occurred at least four times during the evolution of different Drosophila species, and the ability of CYP6G1 to confer resistance to multiple insecticides exists in D. melanogaster and D. simulans but not in Drosophila willistoni or Drosophila virilis. In D. virilis, which has multiple copies of Cyp6g1, one copy confers resistance to DDT and another to nitenpyram, suggesting that the divergence of protein sequence between copies subsequent to the duplication affected the activity of the enzyme. All orthologs tested conferred resistance to one or more insecticides, suggesting that CYP6G1 had the capacity to provide resistance to anthropogenic chemicals before they existed. Finally, we show that expression of Cyp6g1 in the Malpighian tubules, which contributes to DDT resistance in D. melanogaster, is specific to the D. melanogaster-D. simulans lineage. Our results suggest that a combination of gene duplication, regulatory changes and protein coding changes has taken place at the Cyp6g1 locus during evolution and this locus may play a role in providing resistance to different environmental toxins in different Drosophila species.
Kłodowska, Izabella; Rodziewicz, Joanna; Janczukowicz, Wojciech; Gotkowska-Płachta, Anna; Cydzik-Kwiatkowska, Agnieszka
2016-01-01
This work reports on the effect of electric current density and anode material (platinum, carbon) on the concentration of oxidized and mineral forms of nitrogen, on physical parameters (pH, redox potential, electrical conductivity) and the number of denitrifying bacteria in the biofilm (MPN). Experiments were conducted under anaerobic conditions without and with the flow of electric current (with density of 79 mA · m(-2) and 132 mA · m(-2)). Results obtained in the study enabled concluding that increasing density of electric current caused a decreasing concentration of nitrate in the reactor with platinum anode (R1) and carbon anode (R2). Its concentration depended on anode material. The highest hydrogenotrophic denitrification efficiency was achieved in R2 in which the process was aided by inorganic carbon (CO2) that originated from carbon anode oxidation and the electrical conductivity of wastewater increased as a result of the presence of HCO3(-) and CO3(2-) ions. Strong oxidizing properties of the platinum anode (R1) prevented the accumulation of adverse forms of nitrogen, including nitrite and ammonia. The increase in electric current density affected also a lower number of denitrifying bacteria (MPN) in the biofilm in both reactors (R1 and R2). Metal oxides accumulated on the surface of the cathode had a toxic effect upon microorganisms and impaired the production of a hydrogen donor.
Some limit theorems for negatively associated random variables
Indian Academy of Sciences (India)
Abstract. Let {Xn,n ≥ 1} be a sequence of negatively associated random vari- ables. The aim of this paper is to establish some limit theorems of negatively associated sequence, which include the Lp-convergence theorem and Marcinkiewicz–Zygmund strong law of large numbers. Furthermore, we consider the strong law of ...
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Vishal Koparde
Full Text Available Quantitative relationship between the magnitude of variation in minor histocompatibility antigens (mHA and graft versus host disease (GVHD pathophysiology in stem cell transplant (SCT donor-recipient pairs (DRP is not established. In order to elucidate this relationship, whole exome sequencing (WES was performed on 27 HLA matched related (MRD, & 50 unrelated donors (URD, to identify nonsynonymous single nucleotide polymorphisms (SNPs. An average 2,463 SNPs were identified in MRD, and 4,287 in URD DRP (p<0.01; resulting peptide antigens that may be presented on HLA class I molecules in each DRP were derived in silico (NetMHCpan ver2.0 and the tissue expression of proteins these were derived from determined (GTex. MRD DRP had an average 3,670 HLA-binding-alloreactive peptides, putative mHA (pmHA with an IC50 of <500 nM, and URD, had 5,386 (p<0.01. To simulate an alloreactive donor cytotoxic T cell response, the array of pmHA in each patient was considered as an operator matrix modifying a hypothetical cytotoxic T cell clonal vector matrix; each responding T cell clone's proliferation was determined by the logistic equation of growth, accounting for HLA binding affinity and tissue expression of each alloreactive peptide. The resulting simulated organ-specific alloreactive T cell clonal growth revealed marked variability, with the T cell count differences spanning orders of magnitude between different DRP. Despite an estimated, uniform set of constants used in the model for all DRP, and a heterogeneously treated group of patients, higher total and organ-specific T cell counts were associated with cumulative incidence of moderate to severe GVHD in recipients. In conclusion, exome wide sequence differences and the variable alloreactive peptide binding to HLA in each DRP yields a large range of possible alloreactive donor T cell responses. Our findings also help understand the apparent randomness observed in the development of alloimmune responses.
Vassy, Jason L; Christensen, Kurt D; Schonman, Erica F; Blout, Carrie L; Robinson, Jill O; Krier, Joel B; Diamond, Pamela M; Lebo, Matthew; Machini, Kalotina; Azzariti, Danielle R; Dukhovny, Dmitry; Bates, David W; MacRae, Calum A; Murray, Michael F; Rehm, Heidi L; McGuire, Amy L; Green, Robert C
2017-06-27
Whole-genome sequencing (WGS) in asymptomatic adults might prevent disease but increase health care use without clinical value. To describe the effect on clinical care and outcomes of adding WGS to standardized family history assessment in primary care. Pilot randomized trial. (ClinicalTrials.gov: NCT01736566). Academic primary care practices. 9 primary care physicians (PCPs) and 100 generally healthy patients recruited at ages 40 to 65 years. Patients were randomly assigned to receive a family history report alone (FH group) or in combination with an interpreted WGS report (FH + WGS group), which included monogenic disease risk (MDR) results (associated with Mendelian disorders), carrier variants, pharmacogenomic associations, and polygenic risk estimates for cardiometabolic traits. Each patient met with his or her PCP to discuss the report. Clinical outcomes and health care use through 6 months were obtained from medical records and audio-recorded discussions between PCPs and patients. Patients' health behavior changes were surveyed 6 months after receiving results. A panel of clinician-geneticists rated the appropriateness of how PCPs managed MDR results. Mean age was 55 years; 58% of patients were female. Eleven FH + WGS patients (22% [95% CI, 12% to 36%]) had new MDR results. Only 2 (4% [CI, 0.01% to 15%]) had evidence of the phenotypes predicted by an MDR result (fundus albipunctatus due to RDH5 and variegate porphyria due to PPOX). Primary care physicians recommended new clinical actions for 16% (CI, 8% to 30%) of FH patients and 34% (CI, 22% to 49%) of FH + WGS patients. Thirty percent (CI, 17% to 45%) and 41% (CI, 27% to 56%) of FH and FH + WGS patients, respectively, reported making a health behavior change after 6 months. Geneticists rated PCP management of 8 MDR results (73% [CI, 39% to 99%]) as appropriate and 2 results (18% [CI, 3% to 52%]) as inappropriate. Limited sample size and ancestral and socioeconomic diversity. Adding WGS to primary care
Doria, Francesca; Napoli, Chiara; Costantini, Antonella; Berta, Graziella; Saiz, Juan-Carlos; Garcia-Moruno, Emilia
2013-08-01
Malolactic fermentation (MLF) is a biochemical transformation conducted by lactic acid bacteria (LAB) that occurs in wine at the end of alcoholic fermentation. Oenococcus oeni is the main species responsible for MLF in most wines. As in other fermented foods, where bacteriophages represent a potential risk for the fermentative process, O. oeni bacteriophages have been reported to be a possible cause of unsuccessful MLF in wine. Thus, preparation of commercial starters that take into account the different sensitivities of O. oeni strains to different phages would be advisable. However, currently, no methods have been described to identify phages infecting O. oeni. In this study, two factors are addressed: detection and typing of bacteriophages. First, a simple PCR method was devised targeting a conserved region of the endolysin (lys) gene to detect temperate O. oeni bacteriophages. For this purpose, 37 O. oeni strains isolated from Italian wines during different phases of the vinification process were analyzed by PCR for the presence of the lys gene, and 25 strains gave a band of the expected size (1,160 bp). This is the first method to be developed that allows identification of lysogenic O. oeni strains without the need for time-consuming phage bacterial-lysis induction methods. Moreover, a phylogenetic analysis was conducted to type bacteriophages. After the treatment of bacteria with UV light, lysis was obtained for 15 strains, and the 15 phage DNAs isolated were subjected to two randomly amplified polymorphic DNA (RAPD)-PCRs. By combining the RAPD profiles and lys sequences, 12 different O. oeni phages were clearly distinguished.
ajansen; kwhitefoot; panteltje1; edprochak; sudhakar, the
2014-07-01
In reply to the physicsworld.com news story “How to make a quantum random-number generator from a mobile phone” (16 May, http://ow.ly/xFiYc, see also p5), which describes a way of delivering random numbers by counting the number of photons that impinge on each of the individual pixels in the camera of a Nokia N9 smartphone.
Metagenomics using next-generation sequencing.
Bragg, Lauren; Tyson, Gene W
2014-01-01
Traditionally, microbial genome sequencing has been restricted to the small number of species that can be grown in pure culture. The progressive development of culture-independent methods over the last 15 years now allows researchers to sequence microbial communities directly from environmental samples. This approach is commonly referred to as "metagenomics" or "community genomics". However, the term metagenomics is applied liberally in the literature to describe any culture-independent analysis of microbial communities. Here, we define metagenomics as shotgun ("random") sequencing of the genomic DNA of a sample taken directly from the environment. The metagenome can be thought of as a sampling of the collective genome of the microbial community. We outline the considerations and analyses that should be undertaken to ensure the success of a metagenomic sequencing project, including the choice of sequencing platform and methods for assembly, binning, annotation, and comparative analysis.
The autocorrelation structure of Tausworthe pseudorandom number generators
Neuman, F.; Martin, C. F.
1976-01-01
An algorithm for determining the autocorrelation structure of a new sequence generated from an original sequence by proper decimation (a shift with each q-th term of the original sequence used) is presented, once autocorrelations for any repeating number sequence are known. The autocorrelation structure of the Tausworthe random number generator (RNG), based on proper decimation by q, is accepted as a RNG structure in which a proper decimation generates a long interval over which autocorrelations are small for all shifts. It is shown that if L bits of an N-bit Tausworthe RNG are L-bit binary numbers, L + 1 levels of correlation will exist, and L levels of correlation will each occur twice per RNG cycle length.
Pseudorandom number generation using chaotic true orbits of the Bernoulli map
Energy Technology Data Exchange (ETDEWEB)
Saito, Asaki, E-mail: saito@fun.ac.jp [Future University Hakodate, 116-2 Kamedanakano-cho, Hakodate, Hokkaido 041-8655 (Japan); Yamaguchi, Akihiro [Fukuoka Institute of Technology, 3-30-1 Wajiro-higashi, Higashi-ku, Fukuoka 811-0295 (Japan)
2016-06-15
We devise a pseudorandom number generator that exactly computes chaotic true orbits of the Bernoulli map on quadratic algebraic integers. Moreover, we describe a way to select the initial points (seeds) for generating multiple pseudorandom binary sequences. This selection method distributes the initial points almost uniformly (equidistantly) in the unit interval, and latter parts of the generated sequences are guaranteed not to coincide. We also demonstrate through statistical testing that the generated sequences possess good randomness properties.
Number words and number symbols a cultural history of numbers
Menninger, Karl
1992-01-01
Classic study discusses number sequence and language and explores written numerals and computations in many cultures. "The historian of mathematics will find much to interest him here both in the contents and viewpoint, while the casual reader is likely to be intrigued by the author's superior narrative ability.
DEFF Research Database (Denmark)
Kristensen, L E; Christensen, R; Bliddal, H
2007-01-01
To compare the efficacy of adalimumab, etanercept, and infliximab in patients with established rheumatoid arthritis (RA) taking concomitant methotrexate (MTX) by calculating the number needed to treat (NNT) using three different methods....
DEFF Research Database (Denmark)
Kristensen, L E; Christensen, R; Bliddal, H
2011-01-01
To compare the efficacy of adalimumab, etanercept, and infliximab in patients with established rheumatoid arthritis (RA) taking concomitant methotrexate (MTX) by calculating the number needed to treat (NNT) using three different methods.......To compare the efficacy of adalimumab, etanercept, and infliximab in patients with established rheumatoid arthritis (RA) taking concomitant methotrexate (MTX) by calculating the number needed to treat (NNT) using three different methods....
Srichaiya, Arunee; Longchoopol, Chaowanee; Oo-Puthinan, Sarawut; Sayasathid, Jarun; Sripalakit, Pattana; Viyoch, Jarupa
2008-10-01
Lamotrigine is an antiepileptic drug which has been used in the treatment of epilepsy and bipolar disorder. A search of the literature did not find previously published bioequivalence and pharmacokinetic evaluations of lamotrigine in healthy Thai male volunteers. The aim of this study was to compare the pharmacokinetic parameters between 2 brands of lamotrigine in healthy Thai male volunteers. A randomized, single-dose, 2-period, 2-sequence, crossover study design with a 2-week washout period was conducted in healthy Thai males. Subjects were randomized to receive either the test or reference formulation in the first period. All subjects were required to be nonsmokers and without a history of alcohol or drug abuse. Plasma samples were collected over a 120-hour period after 100-mg lamotrigine administration in each period. A validated high-performance liquid chromatography ultraviolet method was used to analyze lamotrigine concentration in plasma. Pharmacokinetic parameters were determined using a noncompartmental method. Bioequivalence between the test and reference products, as defined by the US Food and Drug Administration (FDA), is determined when the ratio for the 90% CIs of the difference in the means of the log-transformed AUC(0-t), AUC(0-infinity), and C(max) of the 2 products are within 0.80 and 1.25. Adverse events were determined by measuring vital signs after dosing. Subjects were also asked if they suffered from undesirable effects such as nausea, vomiting, dizziness, and headache. This bioequivalence study was performed in 24 healthy Thai males (mean [SD] age, 20.5 [1.3] years; range, 19-24 years; weight, 62.5 [7.4] kg; height, 172.8 [6.9] cm; body mass index, 20.9 [2.0] kg/m(2)). The mean (SD) C(max) and T(max) of the test formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.2 (0.9) hours, respectively. The mean (SD) C(max) and T(max) of the reference formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.4 (1.0) hours, respectively. The mean
Directory of Open Access Journals (Sweden)
Wangchao Lou
Full Text Available Developing an efficient method for determination of the DNA-binding proteins, due to their vital roles in gene regulation, is becoming highly desired since it would be invaluable to advance our understanding of protein functions. In this study, we proposed a new method for the prediction of the DNA-binding proteins, by performing the feature rank using random forest and the wrapper-based feature selection using forward best-first search strategy. The features comprise information from primary sequence, predicted secondary structure, predicted relative solvent accessibility, and position specific scoring matrix. The proposed method, called DBPPred, used Gaussian naïve Bayes as the underlying classifier since it outperformed five other classifiers, including decision tree, logistic regression, k-nearest neighbor, support vector machine with polynomial kernel, and support vector machine with radial basis function. As a result, the proposed DBPPred yields the highest average accuracy of 0.791 and average MCC of 0.583 according to the five-fold cross validation with ten runs on the training benchmark dataset PDB594. Subsequently, blind tests on the independent dataset PDB186 by the proposed model trained on the entire PDB594 dataset and by other five existing methods (including iDNA-Prot, DNA-Prot, DNAbinder, DNABIND and DBD-Threader were performed, resulting in that the proposed DBPPred yielded the highest accuracy of 0.769, MCC of 0.538, and AUC of 0.790. The independent tests performed by the proposed DBPPred on completely a large non-DNA binding protein dataset and two RNA binding protein datasets also showed improved or comparable quality when compared with the relevant prediction methods. Moreover, we observed that majority of the selected features by the proposed method are statistically significantly different between the mean feature values of the DNA-binding and the non DNA-binding proteins. All of the experimental results indicate that
Di Girolamo, Guillermo; Czerniuk, Paola; Bertuola, Roberto; Keller, Guillermo A
2010-01-01
Platelet activation is a major component in the pathogenesis of coronary thrombosis and myocardial infarction. Thienopyridines, particularly clopidogrel, are highly effective in reducing in-stent thrombosis and functional inhibition of adenosine diphosphate-induced platelet activation. The aim of this study was to evaluate the bioequivalence of a new generic formulation of clopidogrel 75-mg tablets (test) and the available branded formulation (reference) to meet regulatory criteria for marketing the test product in Argentina. This was a randomized-sequence, open-label, 2-period crossover study conducted in healthy white volunteers in the fasted state. A single oral dose of the test or reference formulation was followed by a 7-day washout period, after which subjects received the alternative formulation. Blood samples were collected at baseline and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after dosing. Clopidogrel concentrations were determined using an LC-MS/MS method. The formulations were considered bioequivalent if the 90% CI of the geometric mean ratios (test:reference) for C(max) and AUC(0-last) were within the range from 80% to 125%. Adverse events were monitored throughout the study based on clinical parameters and patient reports. Twenty-four volunteers (13 male, 11 female; mean [SD] age, 33.7 [5.2] years [range, 21-42 years]; weight, 72.4 [6.83] kg [range, 59-82 kg]) were enrolled in and completed the study. The geometric mean C(max) for the test and reference formulations was 877.76 and 913.49 pg/mL, respectively. The geometric mean AUC(0-t) was 1911.53 and 2053.09 pg . h/mL, and the geometric mean AUC(0-infinity)) was 2021.33 and 2188.25 pg . h/mL. The geometric mean ratios (test:reference) for C(max), AUC(0-t), and AUC(0-infinity)) were 96.09% (90% CI, 90.71-101.78), 93.10% (90% CI, 85.57-101.3), and 92.37% (90% CI, 85.06-100.31), respectively. There were no significant differences in pharmacokinetic parameters between groups
DEFF Research Database (Denmark)
Danielsen, Anne Kjaergaard; Okholm, Cecilie; Pommergaard, Hans-Christian
2014-01-01
BACKGROUND: In general, there is a need for testing new interventions in large randomized controlled trials. Depending on the research question it may be advantageous to establish multicenter studies as a way of organizing clinical trials in order to increase study power. MAIN OBJECTIVES......: The object of this study was to investigate the development in the organization of multicenter studies, the distribution of studies within different clinical specialties, across continents, and investigate the differences related to testing various interventions. METHODS AND MATERIALS: A literature search...
Liu, Xiaoyong; Lu, Pei; Shao, Jianxin; Cao, Haibin; Zhu, Zhenmin
2017-10-01
In this paper, an information hiding method using decimal expansion of irrational numbers to generate random phase mask is proposed. Firstly, the decimal expansion parts of irrational numbers generate pseudo-random sequences using a new coding schemed, the irrational number and start and end bit numbers were used as keys in image information hiding. Secondly, we apply the coding schemed to the double phase encoding system, the pseudo-random sequences are taken to generate random phase masks. The mean square error is used to calculate the quality of the recovered image information. Finally, two tests had been carried out to verify the security of our method; the experimental results demonstrate that the cipher image has such features, strong robustness, key sensitivity, and resistance to brute force attack.
Algebraic polynomials with random coefficients
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K. Farahmand
2002-01-01
Full Text Available This paper provides an asymptotic value for the mathematical expected number of points of inflections of a random polynomial of the form a0(ω+a1(ω(n11/2x+a2(ω(n21/2x2+…an(ω(nn1/2xn when n is large. The coefficients {aj(w}j=0n, w∈Ω are assumed to be a sequence of independent normally distributed random variables with means zero and variance one, each defined on a fixed probability space (A,Ω,Pr. A special case of dependent coefficients is also studied.
Detection of M-Sequences from Spike Sequence in Neuronal Networks
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Yoshi Nishitani
2012-01-01
Full Text Available In circuit theory, it is well known that a linear feedback shift register (LFSR circuit generates pseudorandom bit sequences (PRBS, including an M-sequence with the maximum period of length. In this study, we tried to detect M-sequences known as a pseudorandom sequence generated by the LFSR circuit from time series patterns of stimulated action potentials. Stimulated action potentials were recorded from dissociated cultures of hippocampal neurons grown on a multielectrode array. We could find several M-sequences from a 3-stage LFSR circuit (M3. These results show the possibility of assembling LFSR circuits or its equivalent ones in a neuronal network. However, since the M3 pattern was composed of only four spike intervals, the possibility of an accidental detection was not zero. Then, we detected M-sequences from random spike sequences which were not generated from an LFSR circuit and compare the result with the number of M-sequences from the originally observed raster data. As a result, a significant difference was confirmed: a greater number of “0–1” reversed the 3-stage M-sequences occurred than would have accidentally be detected. This result suggests that some LFSR equivalent circuits are assembled in neuronal networks.
Grešak, Rozalija
2015-01-01
The field of real numbers is usually constructed using Dedekind cuts. In these thesis we focus on the construction of the field of real numbers using metric completion of rational numbers using Cauchy sequences. In a similar manner we construct the field of p-adic numbers, describe some of their basic and topological properties. We follow by a construction of complex p-adic numbers and we compare them with the ordinary complex numbers. We conclude the thesis by giving a motivation for the int...
Improving randomness characterization through Bayesian model selection.
Díaz Hernández Rojas, Rafael; Solís, Aldo; Angulo Martínez, Alí M; U'Ren, Alfred B; Hirsch, Jorge G; Marsili, Matteo; Pérez Castillo, Isaac
2017-06-08
Random number generation plays an essential role in technology with important applications in areas ranging from cryptography to Monte Carlo methods, and other probabilistic algorithms. All such applications require high-quality sources of random numbers, yet effective methods for assessing whether a source produce truly random sequences are still missing. Current methods either do not rely on a formal description of randomness (NIST test suite) on the one hand, or are inapplicable in principle (the characterization derived from the Algorithmic Theory of Information), on the other, for they require testing all the possible computer programs that could produce the sequence to be analysed. Here we present a rigorous method that overcomes these problems based on Bayesian model selection. We derive analytic expressions for a model's likelihood which is then used to compute its posterior distribution. Our method proves to be more rigorous than NIST's suite and Borel-Normality criterion and its implementation is straightforward. We applied our method to an experimental device based on the process of spontaneous parametric downconversion to confirm it behaves as a genuine quantum random number generator. As our approach relies on Bayesian inference our scheme transcends individual sequence analysis, leading to a characterization of the source itself.
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Mohammad Abbasinia
2014-09-01
Full Text Available Introduction: Endotracheal tube suctioning is essential for improve oxygenation in the patients undergoing mechanical ventilation. There are two types of shallow and deep endotracheal tube suctioning. This study aimed to evaluate the effect of shallow and deep suctioning methods on respiratory rate (RR, arterial blood oxygen saturation (SpO2 and number of suctioning in patients hospitalized in the intensive care units of Al-Zahra Hospital, Isfahan, Iran. Methods: In this randomized controlled trial, 74 patients who hospitalized in the intensive care units of Isfahan Al-Zahra Hospital were randomly allocated to the shallow and deep suctioning groups. RR and SpO2 were measured immediately before, immediately after, 1 and 3 minute after each suctioning. Number of suctioning was also noted in each groups. Data were analyzed using repeated measures analysis of variance (RMANOVA, chi-square and independent t-tests. Results: RR was significantly increased and SpO2 was significantly decreased after each suctioning in the both groups. However, these changes were not significant between the two groups. The numbers of suctioning was significantly higher in the shallow suctioning group than in the deep suctioning group. Conclusion: Shallow and deep suctioning had a similar effect on RR and SpO2. However, shallow suctioning caused further manipulation of patient’s trachea than deep suctioning method. Therefore, it seems that deep endotracheal tube suctioning method can be used to clean the airway with lesser manipulation of the trachea.
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Stephanie Medlock
Full Text Available Letters from the hospital to the general practitioner are important for maintaining continuity of care. Although doctors feel letters are important, they are often not written on time. To improve the number and timeliness of letters sent from the hospital outpatient department to the general practitioner using an email-based intervention evaluated in a randomized controlled trial.Users were interviewed to determine the requirements for the intervention. Due to high between-doctor variation at baseline, doctors were matched for baseline performance and pair-randomized. The effectiveness of the intervention was assessed using meta-analytic methods. The primary outcome was the number of patient visits which should have generated a letter that had a letter by 90 days after the visit. Satisfaction was assessed with an anonymous survey.The intervention consisted of a monthly email reminder for each doctor containing a list of his or her patients who were (overdue for a letter. Doctors in the intervention group had 21% fewer patient visits which did not have a letter by 90 days (OR = 5.7, p = 0.0020. Satisfaction with the system was very high.This study examines the effect of a simple reminder in absence of other interventions, and provides an example of an effective non-interruptive decision support intervention.A simple email reminder improved the number and timeliness of letters from the outpatient department to the general practitioner, and was viewed as a useful service by its users.
Murthy, Megha N; Veerappa, Avinash M; Seshachalam, Keshava B; Ramachandra, Nallur B
2016-09-01
Parkinson disease (PD) is a neurological disease responsible for a considerable rate of mortality and morbidity in the society. Since the symptoms of the disease appear much later than the actual onset of neuron degeneration, a majority of cases remain undiagnosed until the manifestation of the symptoms. In order to investigate the existence of such susceptibility in the population, we analyzed Copy Number Variation (CNV) influences on PD genes in 1715 individuals from 12 different populations. Overall, 16 CNV-PD genes, 3 known to be causal and 13 associated, were found to be significantly enriched. PARK2, was under heavy burden with ~1% of the population containing CNV in the exonic region. The impact of these genes on the genome and disease pathway was analyzed using several genome analysis tools. Protein interaction network of CNV-PD genes revealed a complex interaction of molecules forming a major hub by the α-Synuclein, whose direct interactors, LRRK2, PARK2 and ATP13A2 are under CNV influence. We hypothesize that CNVs may not be the initiating event in the pathogenesis of PD and remain latent until additional secondary hits are acquired and also propose novel genes that may fall under the PD pathway which contribute in pathogenesis.
The sequence of sequencers: The history of sequencing DNA
Heather, James M.; Chain, Benjamin
2016-01-01
Determining the order of nucleic acid residues in biological samples is an integral component of a wide variety of research applications. Over the last fifty years large numbers of researchers have applied themselves to the production of techniques and technologies to facilitate this feat, sequencing DNA and RNA molecules. This time-scale has witnessed tremendous changes, moving from sequencing short oligonucleotides to millions of bases, from struggling towards the deduction of the coding sequence of a single gene to rapid and widely available whole genome sequencing. This article traverses those years, iterating through the different generations of sequencing technology, highlighting some of the key discoveries, researchers, and sequences along the way. PMID:26554401
Gironde, S.
2012-01-01
Pseudomonas syringae pv. maculicola causes bacterial spot on Brassicaceae worldwide, and for the last 10 years severe outbreaks have been reported in the Loire Valley, France. P. syringae pv. maculicola resembles P. syringae pv. tomato in that it is also pathogenic for tomato and causes the same types of symptoms. We used a collection of 106 strains of P. syringae to characterize the relationships between P. syringae pv. maculicola and related pathovars, paying special attention to P. syringae pv. tomato. Phylogenetic analysis of gyrB and rpoD gene sequences showed that P. syringae pv. maculicola, which causes diseases in Brassicaceae, forms six genetic lineages within genomospecies 3 of P. syringae strains as defined by L. Gardan et al. (Int. J. Syst. Bacteriol. 49[Pt 2]:469–478, 1999), whereas P. syringae pv. tomato forms two distinct genetic lineages. A multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) conducted with eight minisatellite loci confirmed the genetic structure obtained with rpoD and gyrB sequence analyses. These results provide promising tools for fine-scale epidemiological studies on diseases caused by P. syringae pv. maculicola and P. syringae pv. tomato. The two pathovars had distinct host ranges; only P. syringae pv. maculicola strains were pathogenic for Brassicaceae. A subpopulation of P. syringae pv. maculicola strains that are pathogenic for Pto-expressing tomato plants were shown to lack avrPto1 and avrPtoB or to contain a disrupted avrPtoB homolog. Taking phylogenetic and pathological features into account, our data suggest that the DC3000 strain belongs to P. syringae pv. maculicola. This study shows that P. syringae pv. maculicola and P. syringae pv. tomato appear multiclonal, as they did not diverge from a single common ancestral group within the ancestral P. syringae genomospecies 3, and suggests that pathovar specificity within P. syringae may be due to independent genetic events. PMID:22389364
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JM Ramalho-Ortigão
2001-01-01
Full Text Available Molecular studies of insect disease vectors are of paramount importance for understanding parasite-vector relationship. Advances in this area have led to important findings regarding changes in vectors' physiology upon blood feeding and parasite infection. Mechanisms for interfering with the vectorial capacity of insects responsible for the transmission of diseases such as malaria, Chagas disease and dengue fever are being devised with the ultimate goal of developing transgenic insects. A primary necessity for this goal is information on gene expression and control in the target insect. Our group is investigating molecular aspects of the interaction between Leishmania parasites and Lutzomyia sand flies. As an initial step in our studies we have used random sequencing of cDNA clones from two expression libraries made from head/thorax and abdomen of sugar fed L. longipalpis for the identification of expressed sequence tags (EST. We applied differential display reverse transcriptase-PCR and randomly amplified polymorphic DNA-PCR to characterize differentially expressed mRNA from sugar and blood fed insects, and, in one case, from a L. (V. braziliensis-infected L. longipalpis. We identified 37 cDNAs that have shown homology to known sequences from GeneBank. Of these, 32 cDNAs code for constitutive proteins such as zinc finger protein, glutamine synthetase, G binding protein, ubiquitin conjugating enzyme. Three are putative differentially expressed cDNAs from blood fed and Leishmania-infected midgut, a chitinase, a V-ATPase and a MAP kinase. Finally, two sequences are homologous to Drosophila melanogaster gene products recently discovered through the Drosophila genome initiative.
Number names and number understanding
DEFF Research Database (Denmark)
Ejersbo, Lisser Rye; Misfeldt, Morten
2014-01-01
through using mathematical names for the numbers such as one-ten-one for 11 and five-ten-six for 56. The project combines the renaming of numbers with supporting the teaching with the new number names. Our hypothesis is that Danish children have more difficulties learning and working with numbers, because...
van der Graaf, FHCE; de Jong, BM; Maguire, RP; Meiners, LC; Leenders, KL
We used functional Magnetic Resonance Imaging (fMRI) to examine the distribution of cerebral activation related to prolonged skill practice. In a bimanual variant of the Serial Reaction Time Task (SRT), simultaneous finger movements of the two hands were made in response to randomly ordered pairs of
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Schwarzweller Christoph
2015-02-01
Full Text Available In this article we introduce Proth numbers and prove two theorems on such numbers being prime [3]. We also give revised versions of Pocklington’s theorem and of the Legendre symbol. Finally, we prove Pepin’s theorem and that the fifth Fermat number is not prime.
Vorob'ev, Nikolai Nikolaevich
2011-01-01
Fibonacci numbers date back to an 800-year-old problem concerning the number of offspring born in a single year to a pair of rabbits. This book offers the solution and explores the occurrence of Fibonacci numbers in number theory, continued fractions, and geometry. A discussion of the ""golden section"" rectangle, in which the lengths of the sides can be expressed as a ration of two successive Fibonacci numbers, draws upon attempts by ancient and medieval thinkers to base aesthetic and philosophical principles on the beauty of these figures. Recreational readers as well as students and teacher
Mendonça, J. Ricardo G.
2012-01-01
We define a new class of numbers based on the first occurrence of certain patterns of zeros and ones in the expansion of irracional numbers in a given basis and call them Sagan numbers, since they were first mentioned, in a special case, by the North-american astronomer Carl E. Sagan in his science-fiction novel "Contact." Sagan numbers hold connections with a wealth of mathematical ideas. We describe some properties of the newly defined numbers and indicate directions for further amusement.
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Watase Yasushige
2016-12-01
Full Text Available This article provides definitions and examples upon an integral element of unital commutative rings. An algebraic number is also treated as consequence of a concept of “integral”. Definitions for an integral closure, an algebraic integer and a transcendental numbers [14], [1], [10] and [7] are included as well. As an application of an algebraic number, this article includes a formal proof of a ring extension of rational number field ℚ induced by substitution of an algebraic number to the polynomial ring of ℚ[x] turns to be a field.
Ric, Audrey; Ecochard, Vincent; Iacovoni, Jason S; Boutonnet, Audrey; Ginot, Frédéric; Ong-Meang, Varravaddheay; Poinsot, Véréna; Paquereau, Laurent; Couderc, François
2018-03-01
One of the major difficulties that arises when selecting aptamers containing a G-quadruplex is the correct amplification of the ssDNA sequence. Can aptamers containing a G-quadruplex be selected from a degenerate library using non-equilibrium capillary electrophoresis (CE) of equilibrium mixtures (NECEEM) along with high-throughput Illumina sequencing? In this article, we present some mismatches of the G-quadruplex T29 aptamer specific to thrombin, which was PCR amplified and sequenced by Illumina sequencing. Then, we show the proportionality between the number of sequenced molecules of T29 added to the library and the number of sequences obtained in Illumina sequencing, and we find that T29 sequences from this aptamer can be detected in a random library of ssDNA after the sample is fractionated by NECEEM, amplified by PCR, and sequenced. Treatment of the data by the counting of double-stranded DNA T29 sequences containing a maximum of two mismatches reveals a good correlation with the enrichment factor (f E ). This factor is the ratio of the number of aptamer sequences found in the collected complex sample divided by the total number of sequencing reads (aptamer and non-aptamer) plus the quantity of T29 molecules (spiked into a DNA library) injected into CE.
Cordial Languages and Cordial Numbers
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J. Baskar BABUJEE
2012-01-01
Full Text Available The concept of cordial labeling in graphs motivated us to introduce cordial words, cordial languages and cordial numbers. We interpret the notion of cordial labeling in Automata and thereby study the corresponding languages. In this paper we develop a new sequence of numbers called the cordial numbers in number theory using the labeling techniques in graph theory on automata theory.
Petersen, T Kyle
2015-01-01
This text presents the Eulerian numbers in the context of modern enumerative, algebraic, and geometric combinatorics. The book first studies Eulerian numbers from a purely combinatorial point of view, then embarks on a tour of how these numbers arise in the study of hyperplane arrangements, polytopes, and simplicial complexes. Some topics include a thorough discussion of gamma-nonnegativity and real-rootedness for Eulerian polynomials, as well as the weak order and the shard intersection order of the symmetric group. The book also includes a parallel story of Catalan combinatorics, wherein the Eulerian numbers are replaced with Narayana numbers. Again there is a progression from combinatorics to geometry, including discussion of the associahedron and the lattice of noncrossing partitions. The final chapters discuss how both the Eulerian and Narayana numbers have analogues in any finite Coxeter group, with many of the same enumerative and geometric properties. There are four supplemental chapters throughout, ...
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Sari Agustini Hafman
2013-05-01
Full Text Available According to Kerchoffs (1883, the security system should only rely on cryptographic keys which is used in that system. Generally, the key sequences are generated by a Pseudo Random Number Generator (PRNG or Random Number Generator (RNG. There are three types of randomness sequences that generated by the RNG and PRNG i.e. pseudorandom sequence, cryptographically secure pseudorandom sequences, and real random sequences. Several statistical tests, including diehard battery of tests of randomness, is used to check the type of randomness sequences that generated by PRNG or RNG. Due to its purpose, the principle on taking the testing parameters and the test statistic are associated with the validity of the conclusion produced by a statistical test, then the theoretical analysis is performed by applying a variety of statistical theory to evaluate craps test, one of the test included in the diehard battery of randomness tests. Craps test, inspired by craps game, aims to examine whether a PRNG produces an independent and identically distributed (iid pseudorandom sequences. To demonstrate the process to produce a test statistics equation and to show how craps games applied on that test, will be carried out theoretical analysis by applying a variety of statistical theory. Furthermore, empirical observations will be done by applying craps test on a PRNG in order to check the test effectiveness in detecting the distribution and independency of sequences which produced by PRNG
SPRNG Scalable Parallel Random Number Generator LIbrary
Energy Technology Data Exchange (ETDEWEB)
2010-03-16
This revision corrects some errors in SPRNG 1. Users of newer SPRNG versions can obtain the corrected files and build their version with it. This version also improves the scalability of some of the application-based tests in the SPRNG test suite. It also includes an interface to a parallel Mersenne Twister, so that if users install the Mersenne Twister, then they can test this generator with the SPRNG test suite and also use some SPRNG features with that generator.
Random Number Generation: A Practitioner's Overview
CERN. Geneva
2012-01-01
About the speaker Dr. Mascagni is full professor at Florida State University, where he runs a research group consisting of post-doctoral associates, graduate students, and undergraduate workers. The areas they work on are p...
Random Number Generation for High Performance Computing
2015-01-01
issued patent and patent application are included as appendices in the pdf file accompanying this final report. Received Book TOTAL: Received Book Chapter...plan, the product of research undertaken by Silicon Informatics, KEYW Corporation and the UTSA Center for Innovation and Technology Entrepreneurship
Directory of Open Access Journals (Sweden)
Roghaie Khoshkholgh
2016-05-01
Full Text Available Objective: To compare the effects of two auditory methods by mother and fetus on the results of NST in 2011-2012.Materials and methods: In this single-blind clinical trial, 213 pregnant women with gestational age of 37-41 weeks who had no pregnancy complications were randomly divided into 3 groups (auditory intervention for mother, auditory intervention for fetus, and control each containing 71 subjects. In the intervention groups, music was played through the second 10 minutes of NST. The three groups were compared regarding baseline fetal heart rate and number of accelerations in the first and second 10 minutes of NST. The data were analyzed using one-way ANOVA, Kruskal-Wallis, and paired T-test.Results: The results showed no significant difference among the three groups regarding baseline fetal heart rate in the first (p = 0.945 and second (p = 0.763 10 minutes. However, a significant difference was found among the three groups concerning the number of accelerations in the second 10 minutes. Also, a significant difference was observed in the number of accelerations in the auditory intervention for mother (p = 0.013 and auditory intervention for fetus groups (p < 0.001. The difference between the number of accelerations in the first and second 10 minutes was also statistically significant (p = 0.002.Conclusion: Music intervention was effective in the number of accelerations which is the indicator of fetal health. Yet, further studies are required to be conducted on the issue.
Chiva-Blanch, Gemma; Condines, Ximena; Magraner, Emma; Roth, Irene; Valderas-Martínez, Palmira; Arranz, Sara; Casas, Rosa; Martínez-Huélamo, Miriam; Vallverdú-Queralt, Anna; Quifer-Rada, Paola; Lamuela-Raventos, Rosa M; Estruch, Ramon
2014-04-01
Moderate alcohol consumption is associated with a decrease in cardiovascular risk, but fermented beverages seem to confer greater cardiovascular protection due to their polyphenolic content. Circulating endothelial progenitor cells (EPC) are bone-marrow-derived stem cells with the ability to repair and maintain endothelial integrity and function and are considered as a surrogate marker of vascular function and cumulative cardiovascular risk. Nevertheless, no study has been carried out on the effects of moderate beer consumption on the number of circulating EPC in high cardiovascular risk patients. To compare the effects of moderate consumption of beer, non-alcoholic beer and gin on the number of circulating EPC and EPC-mobilizing factors. In this crossover trial, 33 men at high cardiovascular risk were randomized to receive beer (30 g alcohol/d), the equivalent amount of polyphenols in the form of non-alcoholic beer, or gin (30 g alcohol/d) for 4 weeks. Diet and physical exercise were carefully monitored. The number of circulating EPC and EPC-mobilizing factors were determined at baseline and after each intervention. After the beer and non-alcoholic beer interventions, the number of circulating EPC significantly increased by 8 and 5 units, respectively, while no significant differences were observed after the gin period. In correlation, stromal cell derived factor 1 increased significantly after the non-alcoholic and the beer interventions. The non-alcoholic fraction of beer increases the number of circulating EPC in peripheral blood from high cardiovascular risk subjects. http://www.controlled-trials.com/ISRCTN95345245 ISRCTN95345245. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Andrews, George E
1994-01-01
Although mathematics majors are usually conversant with number theory by the time they have completed a course in abstract algebra, other undergraduates, especially those in education and the liberal arts, often need a more basic introduction to the topic.In this book the author solves the problem of maintaining the interest of students at both levels by offering a combinatorial approach to elementary number theory. In studying number theory from such a perspective, mathematics majors are spared repetition and provided with new insights, while other students benefit from the consequent simpl
Helleloid, Geir; Khalid, Madeeha; Moulton, David Petrie; Wood, Philip Matchett
2008-01-01
In graph pegging, we view each vertex of a graph as a hole into which a peg can be placed, with checker-like ``pegging moves'' allowed. Motivated by well-studied questions in graph pebbling, we introduce two pegging quantities. The pegging number (respectively, the optimal pegging number) of a graph is the minimum number of pegs such that for every (respectively, some) distribution of that many pegs on the graph, any vertex can be reached by a sequence of pegging moves. We prove several basic...
Barnes, John
2016-01-01
In this intriguing book, John Barnes takes us on a journey through aspects of numbers much as he took us on a geometrical journey in Gems of Geometry. Similarly originating from a series of lectures for adult students at Reading and Oxford University, this book touches a variety of amusing and fascinating topics regarding numbers and their uses both ancient and modern. The author intrigues and challenges his audience with both fundamental number topics such as prime numbers and cryptography, and themes of daily needs and pleasures such as counting one's assets, keeping track of time, and enjoying music. Puzzles and exercises at the end of each lecture offer additional inspiration, and numerous illustrations accompany the reader. Furthermore, a number of appendices provides in-depth insights into diverse topics such as Pascal’s triangle, the Rubik cube, Mersenne’s curious keyboards, and many others. A theme running through is the thought of what is our favourite number. Written in an engaging and witty sty...
Directory of Open Access Journals (Sweden)
Gur Yaari
Full Text Available The long lasting debate initiated by Gilovich, Vallone and Tversky in [Formula: see text] is revisited: does a "hot hand" phenomenon exist in sports? Hereby we come back to one of the cases analyzed by the original study, but with a much larger data set: all free throws taken during five regular seasons ([Formula: see text] of the National Basketball Association (NBA. Evidence supporting the existence of the "hot hand" phenomenon is provided. However, while statistical traces of this phenomenon are observed in the data, an open question still remains: are these non random patterns a result of "success breeds success" and "failure breeds failure" mechanisms or simply "better" and "worse" periods? Although free throws data is not adequate to answer this question in a definite way, we speculate based on it, that the latter is the dominant cause behind the appearance of the "hot hand" phenomenon in the data.
Weight Distributions for Turbo Codes Using Random and Nonrandom Permutations
Dolinar, S.; Divsalar, D.
1995-04-01
This article takes a preliminary look at the weight distributions achievable for turbo codes using random, nonrandom, and semirandom permutations. Due to the recursiveness of the encoders, it is important to distinguish between self-terminating and non-self-terminating input sequences. The non-self-terminating sequences have little effect on decoder performance, because they accumulate high encoded weight until they are artificially terminated at the end of the block. From probabilistic arguments based on selecting the permutations randomly, it is concluded that the self-terminating weight-2 data sequences are the most important consideration in the design of the constituent codes; higher-weight self-terminating sequences have successively decreasing importance. Also, increasing the number of codes and, correspondingly, the number of permutations makes it more and more likely that the bad input sequences will be broken up by one or more of the permuters. It is possible to design nonrandom permutations that ensure that the minimum distance due to weight-2 input sequences grows roughly as p 2N, where N is the block length. However, these nonrandom permutations amplify the bad effects of higher-weight inputs, and as a result they are inferior in performance to randomly selected permutations. But there are "semirandom" permutations that perform nearly as well as the designed nonrandom permutations with respect to weight-2 input sequences and are not as susceptible to being foiled by higher-weight inputs.
Cryptography, statistics and pseudo-randomness (Part 1)
Brands, S.; Gill, R.D.
1995-01-01
In the classical approach to pseudo-random number generators, a generator is considered to perform well if its output sequences pass a battery of statistical tests that has become standard. In recent years, it has turned out that this approach is not satisfactory. Many generators have turned out to
Directory of Open Access Journals (Sweden)
Theodore M. Porter
2012-12-01
Full Text Available The struggle over cure rate measures in nineteenth-century asylums provides an exemplary instance of how, when used for official assessments of institutions, these numbers become sites of contestation. The evasion of goals and corruption of measures tends to make these numbers “funny” in the sense of becoming dis-honest, while the mismatch between boring, technical appearances and cunning backstage manipulations supplies dark humor. The dangers are evident in recent efforts to decentralize the functions of governments and corporations using incen-tives based on quantified targets.
Energy Technology Data Exchange (ETDEWEB)
Lavrov, Dennis V.; Boore, Jeffrey L.; Brown, Wesley M.
2001-11-08
We determined the complete mtDNA sequences of the millipedes Narceus annularus and Thyropygus sp. (Arthropoda: Diplopoda) and identified in both genomes all 37 genes typical for metazoan mtDNA. The arrangement of these genes is identical in the two millipedes, but differs from that inferred to be ancestral for arthropods by the location of four genes/gene clusters. This novel gene arrangement is unusual for animal mtDNA, in that genes with opposite transcriptional polarities are clustered in the genome and the two clusters are separated by two non-coding regions. The only exception to this pattern is the gene for cysteine tRNA, which is located in the part of the genome that otherwise contains all genes with the opposite transcriptional polarity. We suggest that a mechanism involving complete mtDNA duplication followed by the loss of genes, predetermined by their transcriptional polarity and location in the genome, could generate this gene arrangement from the one ancestral for arthropods. The proposed mechanism has important implications for phylogenetic inferences that are drawn on the basis of gene arrangement comparisons.
Indian Academy of Sciences (India)
How many points are there on a line? Which is more in number- points on a line or lines in a plane? These are some natural questions that have occurred to us sometime or the other. It is interesting to note the difference between the two questions. Do we have to know how many points and lines there are to answer.
Indian Academy of Sciences (India)
Admin
Left: Anuradha S Garge completed her PhD from. Pune University in 2008 under the supervision of Prof. S A Katre. Her research interests include K-theory and number theory. Besides mathematics, she is interested in (singing) indian classical music and yoga. Right: Shailesh Shirali is. Director of Sahyadri School.
Psychoacoustic Properties of Fibonacci Sequences
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J. Sokoll
2008-01-01
Full Text Available 1202, Fibonacci set up one of the most interesting sequences in number theory. This sequence can be represented by so-called Fibonacci Numbers, and by a binary sequence of zeros and ones. If such a binary Fibonacci Sequence is played back as an audio file, a very dissonant sound results. This is caused by the “almost-periodic”, “self-similar” property of the binary sequence. The ratio of zeros and ones converges to the golden ratio, as do the primary and secondary spectral components intheir frequencies and amplitudes. These Fibonacci Sequences will be characterized using listening tests and psychoacoustic analyses.
Directory of Open Access Journals (Sweden)
Xinguang Chen
Full Text Available Mobile populations and men who have sex with men (MSM play an increasing role in the current HIV epidemic in China and across the globe. While considerable research has addressed both of these at-risk populations, more effective HIV control requires accurate data on the number of MSM at the population level, particularly MSM among migrant populations.Survey data from a random sample of male rural-to-urban migrants (aged 18-45, n=572 in Wuhan, China were analyzed and compared with those of randomly selected non-migrant urban (n=566 and rural counterparts (580. The GIS/GPS technologies were used for sampling and the survey estimation method was used for data analysis.HIV-related risk behaviors among rural-to-urban migrants were similar to those among the two comparison groups. The estimated proportion of MSM among migrants [95% CI] was 5.8% [4.7, 6.8], higher than 2.8% [1.2, 4.5] for rural residents and 1.0% [0.0, 2.4] for urban residents, respectively. Among these migrants, the MSM were more likely than non-MSM to be older in age, married, and migrated to more cities. They were also more likely to co-habit with others in rental properties located in new town and neighborhoods with fewer old acquaintances and more entertainment establishments. In addition, they were more likely to engage in commercial sex and less likely to consistently use condoms.Findings of this study indicate that compared to rural and urban populations, the migrant population in Wuhan consists of a higher proportion of MSM who also exhibit higher levels of HIV-related risk behaviors. More effective interventions should target this population with a focus on neighborhood factors, social capital and collective efficacy for risk reduction.
A P-N Sequence Generator Using LFSR with Dual Edge Trigger Technique
Naghwal Nitin Kumar; Kumar Abhishek
2016-01-01
This paper represents the design and implementation of a low power 4-bit LFSR using Dual edge triggered flip flop. A linear feedback shift register (LFSR) is assembled by N number of flip flops connected in series and a combinational logic generally xor gate. An LFSR can generate random number sequence which acts as cipher in cryptography. A known text encrypted over long PN sequence, in order to improve security sequence made longer ie 128 bit; require long chain of flip flop leads to more p...
Curling Numbers of Certain Graph Powers
C, Susanth; Kalayathankal, Sunny Joseph; Sudev, N. K.; Chithra, K. P.; Kok, Johan
2015-01-01
Given a finite nonempty sequence $S$ of integers, write it as $XY^k$, where $Y^k$ is a power of greatest exponent that is a suffix of $S$: this $k$ is the curling number of $S$. The concept of curling number of sequences has already been extended to the degree sequences of graphs to define the curling number of a graph. In this paper we study the curling number of graph powers, graph products and certain other graph operations.
Number names and number understanding
DEFF Research Database (Denmark)
Ejersbo, Lisser Rye; Misfeldt, Morten
2014-01-01
This paper concerns the results from the first year of a three-year research project involving the relationship between Danish number names and their corresponding digits in the canonical base 10 system. The project aims to develop a system to help the students’ understanding of the base 10 syste...
Energy Technology Data Exchange (ETDEWEB)
Dotsenko, Viktor S [Landau Institute for Theoretical Physics, Russian Academy of Sciences, Moscow (Russian Federation)
2011-03-31
In the last two decades, it has been established that a single universal probability distribution function, known as the Tracy-Widom (TW) distribution, in many cases provides a macroscopic-level description of the statistical properties of microscopically different systems, including both purely mathematical ones, such as increasing subsequences in random permutations, and quite physical ones, such as directed polymers in random media or polynuclear crystal growth. In the first part of this review, we use a number of models to examine this phenomenon at a simple qualitative level and then consider the exact solution for one-dimensional directed polymers in a random environment, showing that free energy fluctuations in such a system are described by the universal TW distribution. The second part provides detailed appendix material containing the necessary mathematical background for the first part. (reviews of topical problems)
Genome Sequence Databases (Overview): Sequencing and Assembly
Energy Technology Data Exchange (ETDEWEB)
Lapidus, Alla L.
2009-01-01
From the date its role in heredity was discovered, DNA has been generating interest among scientists from different fields of knowledge: physicists have studied the three dimensional structure of the DNA molecule, biologists tried to decode the secrets of life hidden within these long molecules, and technologists invent and improve methods of DNA analysis. The analysis of the nucleotide sequence of DNA occupies a special place among the methods developed. Thanks to the variety of sequencing technologies available, the process of decoding the sequence of genomic DNA (or whole genome sequencing) has become robust and inexpensive. Meanwhile the assembly of whole genome sequences remains a challenging task. In addition to the need to assemble millions of DNA fragments of different length (from 35 bp (Solexa) to 800 bp (Sanger)), great interest in analysis of microbial communities (metagenomes) of different complexities raises new problems and pushes some new requirements for sequence assembly tools to the forefront. The genome assembly process can be divided into two steps: draft assembly and assembly improvement (finishing). Despite the fact that automatically performed assembly (or draft assembly) is capable of covering up to 98% of the genome, in most cases, it still contains incorrectly assembled reads. The error rate of the consensus sequence produced at this stage is about 1/2000 bp. A finished genome represents the genome assembly of much higher accuracy (with no gaps or incorrectly assembled areas) and quality ({approx}1 error/10,000 bp), validated through a number of computer and laboratory experiments.
Cluster-Based Multipolling Sequencing Algorithm for Collecting RFID Data in Wireless LANs
Choi, Woo-Yong; Chatterjee, Mainak
2015-03-01
With the growing use of RFID (Radio Frequency Identification), it is becoming important to devise ways to read RFID tags in real time. Access points (APs) of IEEE 802.11-based wireless Local Area Networks (LANs) are being integrated with RFID networks that can efficiently collect real-time RFID data. Several schemes, such as multipolling methods based on the dynamic search algorithm and random sequencing, have been proposed. However, as the number of RFID readers associated with an AP increases, it becomes difficult for the dynamic search algorithm to derive the multipolling sequence in real time. Though multipolling methods can eliminate the polling overhead, we still need to enhance the performance of the multipolling methods based on random sequencing. To that extent, we propose a real-time cluster-based multipolling sequencing algorithm that drastically eliminates more than 90% of the polling overhead, particularly so when the dynamic search algorithm fails to derive the multipolling sequence in real time.
Energy Technology Data Exchange (ETDEWEB)
Foley, Brian Thomas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Leitner, Thomas Kenneth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Apetrei, Cristian [Univ. of Pittsburgh, PA (United States); Hahn, Beatrice [Univ. of Pennsylvania, Philadelphia, PA (United States); Mizrachi, Ilene [National Center for Biotechnology Information, Bethesda, MD (United States); Mullins, James [Univ. of Washington, Seattle, WA (United States); Rambaut, Andrew [Univ. of Edinburgh, Scotland (United Kingdom); Wolinsky, Steven [Northwestern Univ., Evanston, IL (United States); Korber, Bette Tina Marie [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
2015-10-05
This compendium is an annual printed summary of the data contained in the HIV sequence database. We try to present a judicious selection of the data in such a way that it is of maximum utility to HIV researchers. Each of the alignments attempts to display the genetic variability within the different species, groups and subtypes of the virus. This compendium contains sequences published before January 1, 2015. Hence, though it is published in 2015 and called the 2015 Compendium, its contents correspond to the 2014 curated alignments on our website. The number of sequences in the HIV database is still increasing. In total, at the end of 2014, there were 624,121 sequences in the HIV Sequence Database, an increase of 7% since the previous year. This is the first year that the number of new sequences added to the database has decreased compared to the previous year. The number of near complete genomes (>7000 nucleotides) increased to 5834 by end of 2014. However, as in previous years, the compendium alignments contain only a fraction of these. A more complete version of all alignments is available on our website, http://www.hiv.lanl.gov/ content/sequence/NEWALIGN/align.html As always, we are open to complaints and suggestions for improvement. Inquiries and comments regarding the compendium should be addressed to seq-info@lanl.gov.
On Lacunary Mean Ideal Convergence in Generalized Random n-Normed Spaces
Directory of Open Access Journals (Sweden)
Awad A. Bakery
2014-01-01
Full Text Available An ideal I is a hereditary and additive family of subsets of positive integers ℕ. In this paper, we will introduce the concept of generalized random n-normed space as an extension of random n-normed space. Also, we study the concept of lacunary mean (L-ideal convergence and L-ideal Cauchy for sequences of complex numbers in the generalized random n-norm. We introduce IL-limit points and IL-cluster points. Furthermore, Cauchy and IL-Cauchy sequences in this construction are given. Finally, we find relations among these concepts.
Sequence Factorial and Its Applications
Asiru, Muniru A.
2012-01-01
In this note, we introduce sequence factorial and use this to study generalized M-bonomial coefficients. For the sequence of natural numbers, the twin concepts of sequence factorial and generalized M-bonomial coefficients, respectively, extend the corresponding concepts of factorial of an integer and binomial coefficients. Some latent properties…
Zou, Jianjun; Di, Bin; Wu, Chun Yong; Hu, Qin; Li, Jian Hua; Zhu, Yubing; Fan, Hongwei; Xiao, DaWei; Wang, Guang Ji
2008-04-01
Cefteram pivoxil (CFTM-PI) is an oral antibiotic available in powder suspension and tablet formulations indicated in China for the treatment of bacterial infections. Although these 2 formulations are marketed in China, published information regarding their pharmacokinetics and bioequivalence in the Chinese population is not available. The aim of this study was to compare the pharmacokinetics and bioequivalence of the powder suspension (test) and tablet (reference) formulations of CFTM-PI 100 mg available in China. This single-dose, randomized-sequence, open-label, 2-period crossover study was performed at the Nanjing First Hospital of Nanjing Medical University. Eligible subjects were healthy male volunteers who were randomly assigned at a 1:1 ratio to receive a single 100-mg dose of the test or reference formulation, followed by a 1-week washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. Plasma was assayed using a high-performance liquid chromatography method. For analysis of pharmacokinetic properties, including C(max), AUC from time 0 (baseline) to 6 hours (AUC(0-6)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were obtained at intervals over the 6-hour period after study drug administration. The formulations were considered bioequivalent if the log-transformed ratios of C(max) and AUC were within the predetermined equivalence range (80%-125%) as established by the US Food and Drug Administration (FDA). Tolerability was assessed by monitoring vital signs and laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis), and by questioning subjects about adverse events (AEs). Twenty-four Chinese male subjects (mean [range] age,24.2 [23-32] years;weight,64.3 [58-67] kg; height, 172 [167-185] cm) enrolled; all completed the study. No period or sequence effect was observed. The 90% CIs for the log-transformed ratios of C(max), AUC(0-6;), and
Zhu, YuBing; Zou, JianJun; Xiao, DaWei; Fan, HongWei; Yu, CuiXia; Zhang, JingJing; Yang, Jing; Guo, DaQing
2009-07-01
Glucosamine sulfate is used for the treatment of arthrosis, especially osteoarthritis of the knee joint. The available evidence suggests differences in its pharmacokinetics in Chinese subjects compared with non-Chinese subjects. The aim of this study was to compare the pharmacokinetics and relative bioavailability of a test and reference formulation of glucosamine sulfate 500 mg after single oral administration in healthy Chinese volunteers. This open-label, randomized-sequence, single-dose, 2-way crossover study was performed at the First Hospital of Nanjing Medical University, Nanjing, China. Eligible subjects were healthy male volunteers who were randomly assigned at a 1:1 ratio to receive a single 500-mg dose of the test or reference capsule formulation, followed by a 1-week washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. Glucosamine sulfate was assayed using a liquid-chromatography tandem mass spectrometry method. For analysis of pharmacokinetic properties, including C(max), AUC(0-t), and AUC(0-infinity)), blood samples were obtained at intervals over a 14-hour period after study drug administration. The formulations were considered bioequivalent if the log-transformed ratios of C(max) and AUC were within the predetermined equivalence range (70%-143% for C(max) and 80%-125% for AUC) as established by the State Food and Drug Administration (SFDA) of China. Tolerability was assessed by monitoring vital signs and laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis), and by questioning subjects about adverse events (AEs). Twenty-two healthy male Chinese subjects were enrolled (mean [range] age, 24 [22-26] years; weight, 63.9 [58.5-69.3] kg; height, 172 [167-177] cm); all completed the study. No period or sequence effect was observed. The 90% CIs for the log-transformed ratios of C(max), AUC(0-t), and AUC(0-infinity)) were 93.4 to 127.3, 92.4 to 114
DEFF Research Database (Denmark)
Sato, Shusei; Andersen, Stig Uggerhøj
2014-01-01
The current Lotus japonicus reference genome sequence is based on a hybrid assembly of Sanger TAC/BAC, Sanger shotgun and Illumina shotgun sequencing data generated from the Miyakojima-MG20 accession. It covers nearly all expressed L. japonicus genes and has been annotated mainly based...... on transcriptional evidence. Analysis of repetitive sequences suggests that they are underrepresented in the reference assembly, reflecting an enrichment of gene-rich regions in the current assembly. Characterization of Lotus natural variation by resequencing of L. japonicus accessions and diploid Lotus species...... is currently ongoing, facilitated by the MG20 reference sequence...
Jamieson, F B; Teatero, S; Guthrie, J L; Neemuchwala, A; Fittipaldi, N; Mehaffy, C
2014-10-01
Mycobacterium tuberculosis isolates of the Manila sublineage are genetically homogeneous. In this study, we used whole-genome sequencing (WGS) to type a collection of 36 M. tuberculosis isolates of the Manila family. WGS enabled the subtyping of these 36 isolates into at least 10 distinct clusters. Our results indicate that WGS is a powerful approach to determining the relatedness of Manila family M. tuberculosis isolates. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
PHARMACOGENETIC TESTING OPPORTUNITIES IN CARDIOLOGY BASED ON EXOME SEQUENCING
Directory of Open Access Journals (Sweden)
N. V. Shcherbakova
2014-01-01
Full Text Available Aim. To study what cardiac drugs currently have any comments on biomarkers and what information can be obtained by pharmacogenetic testing using data exome sequencing in patients with cardiac diseases.Material and methods. Exome sequencing in random participant of the ATEROGEN IVANOVO study and bioinformatics analysis of the data were performed. Point mutations were annotated using ANNOVAR program, as well as comparison with a number of specialized databases was done on the basis of user protocols.Results. 11 cardiac drugs and 7 genes which variants can influence cardiac drug metabolism were analyzed. According to exome sequencing of the participant we did not reveal allelic variants that require dose regime correction and careful efficacy control.Conclusion. The exome sequencing application is the next step to a wide range of personalized therapy. Future opportunities for improvement of the risk-benefit ratio in each patient are the main purpose of the collection and analysis of pharmacogenetic data.
Directory of Open Access Journals (Sweden)
Morteza Shojaei Moghadam
2010-01-01
Full Text Available Six strains of bacteriocinogenic Lactobacillus plantarum (TL1, RG11, RS5, UL4, RG14 and RI11 isolated from Malaysian foods were investigated for their structural bacteriocin genes. A new combination of plantaricin EF and plantaricin W bacteriocin structural genes was successfully amplified from all studied strains, suggesting that they were novel bacteriocin-producing L. plantarum strains. A four-base pair variable region was detected in the short 16S-23S intergenic spacer regions of the studied strains by a comparative analysis with 17 L. plantarum strains deposited in the GenBank, implying they were new genotypes. The studied L. plantarum strains were subsequently differentiated into four groups on the basis of the detected four-base pair variable region of the short 16S-23S intergenic spacer region. Further analysis of the DNA sequence of 23S-5S intergenic spacer region revealed only one type of 23S-5S intergenic spacer region present in the studied strains, indicating it was highly conserved among the studied L. plantarum strains. Three randomly amplified polymorphic DNA experiments using three different combinations of arbitrary primers successfully differentiated the studied L. plantarum strains from each other, confirming they were different strains. In conclusion, the studied L. plantarum strains were shown to be novel bacteriocin producers and high level of strain discrimination could be achieved with a combination of randomly amplified polymorphic DNA analysis and the analysis of the variable region of short 16S-23S intergenic spacer region present in L. plantarum strains.
EPCGen2 pseudorandom number generators: analysis of J3Gen.
Peinado, Alberto; Munilla, Jorge; Fúster-Sabater, Amparo
2014-04-09
This paper analyzes the cryptographic security of J3Gen, a promising pseudo random number generator for low-cost passive Radio Frequency Identification (RFID) tags. Although J3Gen has been shown to fulfill the randomness criteria set by the EPCglobal Gen2 standard and is intended for security applications, we describe here two cryptanalytic attacks that question its security claims: (i) a probabilistic attack based on solving linear equation systems; and (ii) a deterministic attack based on the decimation of the output sequence. Numerical results, supported by simulations, show that for the specific recommended values of the configurable parameters, a low number of intercepted output bits are enough to break J3Gen. We then make some recommendations that address these issues.
EPCGen2 Pseudorandom Number Generators: Analysis of J3Gen
Directory of Open Access Journals (Sweden)
Alberto Peinado
2014-04-01
Full Text Available This paper analyzes the cryptographic security of J3Gen, a promising pseudo random number generator for low-cost passive Radio Frequency Identification (RFID tags. Although J3Gen has been shown to fulfill the randomness criteria set by the EPCglobal Gen2 standard and is intended for security applications, we describe here two cryptanalytic attacks that question its security claims: (i a probabilistic attack based on solving linear equation systems; and (ii a deterministic attack based on the decimation of the output sequence. Numerical results, supported by simulations, show that for the specific recommended values of the configurable parameters, a low number of intercepted output bits are enough to break J3Gen. We then make some recommendations that address these issues.
Niglio de Figueiredo, Marcelo; Rudolph, Bärbel; Rodolph, Bärbel; Bylund, Carma L; Goelz, Tanja; Heußner, Pia; Sattel, Heribert; Fritzsche, Kurt; Wuensch, Alexander
2015-07-07
Communication skills training has proven to be an effective means to enhance communication of health care professionals in oncology. These effects are well studied in standardized settings. The question of transferring these skills into clinical consultations remains open. We build up on a previous developed training concept consisting of a workshop and coaching. This training achieved a medium effect size in two studies with standardized patients. In the current study, we expanded and manualized the coaching concept, and we will evaluate effects of a varied number of coaching sessions on real clinical consultations. Our aim is to determine how much coaching oncologists need to transfer communication skills into clinical practice. Physicians of two German medical centers will participate in a workshop for communication skills and will be randomized to either a group with one coaching session or a group with four coaching sessions following the workshop. The participation is voluntary and the physicians will receive medical education points. Consultations held by the participating physicians with actual patients who gave their informed consent will be filmed at three time points. These consultations will be evaluated by blinded raters using a checklist based on the training content (primary outcome). Secondary outcomes will be the self-evaluated communication competence by physicians and an evaluation of the consultations by both physicians and patients. We will evaluate our communication training concept on three levels - rater, physician and patient - and concentrate on the transfer of communication skills into real life situations. As we emphasize the external validity in this study design, limitations will be expected due to heterogeneity of data. With this study we aim to gain data on how to improve communication skills training that will result in better patient outcomes. German Clinical Trials Register DRKS00004385 .
PREDICTION OF CHROMATIN STATES USING DNA SEQUENCE PROPERTIES
Bahabri, Rihab R.
2013-06-01
Activities of DNA are to a great extent controlled epigenetically through the internal struc- ture of chromatin. This structure is dynamic and is influenced by different modifications of histone proteins. Various combinations of epigenetic modification of histones pinpoint to different functional regions of the DNA determining the so-called chromatin states. How- ever, the characterization of chromatin states by the DNA sequence properties remains largely unknown. In this study we aim to explore whether DNA sequence patterns in the human genome can characterize different chromatin states. Using DNA sequence motifs we built binary classifiers for each chromatic state to eval- uate whether a given genomic sequence is a good candidate for belonging to a particular chromatin state. Of four classification algorithms (C4.5, Naive Bayes, Random Forest, and SVM) used for this purpose, the decision tree based classifiers (C4.5 and Random Forest) yielded best results among those we evaluated. Our results suggest that in general these models lack sufficient predictive power, although for four chromatin states (insulators, het- erochromatin, and two types of copy number variation) we found that presence of certain motifs in DNA sequences does imply an increased probability that such a sequence is one of these chromatin states.
Interpolation of missing data in image sequences.
Kokaram, A C; Morris, R D; Fitzgerald, W J; Rayner, P W
1995-01-01
This paper presents a number of model based interpolation schemes tailored to the problem of interpolating missing regions in image sequences. These missing regions may be of arbitrary size and of random, but known, location. This problem occurs regularly with archived film material. The film is abraded or obscured in patches, giving rise to bright and dark flashes, known as "dirt and sparkle" in the motion picture industry. Both 3-D autoregressive models and 3-D Markov random fields are considered in the formulation of the different reconstruction processes. The models act along motion directions estimated using a multiresolution block matching scheme. It is possible to address this sort of impulsive noise suppression problem with median filters, and comparisons with earlier work using multilevel median filters are performed. These comparisons demonstrate the higher reconstruction fidelity of the new interpolators.
Alternation Blindness in the Representation of Binary Sequences.
Yu, Ru Qi; Osherson, Daniel; Zhao, Jiaying
2017-08-17
Binary information is prevalent in the environment and contains 2 distinct outcomes. Binary sequences consist of a mixture of alternation and repetition. Understanding how people perceive such sequences would contribute to a general theory of information processing. In this study, we examined how people process alternation and repetition in binary sequences. Across 4 paradigms involving estimation, working memory, change detection, and visual search, we found that the number of alternations is underestimated compared with repetitions (Experiment 1). Moreover, recall for binary sequences deteriorates as the sequence alternates more (Experiment 2). Changes in bits are also harder to detect as the sequence alternates more (Experiment 3). Finally, visual targets superimposed on bits of a binary sequence take longer to process as alternation increases (Experiment 4). Overall, our results indicate that compared with repetition, alternation in a binary sequence is less salient in the sense of requiring more attention for successful encoding. The current study thus reveals the cognitive constraints in the representation of alternation and provides a new explanation for the overalternation bias in randomness perception. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Transposon facilitated DNA sequencing
Energy Technology Data Exchange (ETDEWEB)
Berg, D.E.; Berg, C.M.; Huang, H.V.
1990-01-01
The purpose of this research is to investigate and develop methods that exploit the power of bacterial transposable elements for large scale DNA sequencing: Our premise is that the use of transposons to put primer binding sites randomly in target DNAs should provide access to all portions of large DNA fragments, without the inefficiencies of methods involving random subcloning and attendant repetitive sequencing, or of sequential synthesis of many oligonucleotide primers that are used to match systematically along a DNA molecule. Two unrelated bacterial transposons, Tn5 and {gamma}{delta}, are being used because they have both proven useful for molecular analyses, and because they differ sufficiently in mechanism and specificity of transposition to merit parallel development.
What's Next? Judging Sequences of Binary Events
Oskarsson, An T.; Van Boven, Leaf; McClelland, Gary H.; Hastie, Reid
2009-01-01
The authors review research on judgments of random and nonrandom sequences involving binary events with a focus on studies documenting gambler's fallacy and hot hand beliefs. The domains of judgment include random devices, births, lotteries, sports performances, stock prices, and others. After discussing existing theories of sequence judgments,…
Energy Technology Data Exchange (ETDEWEB)
Kuiken, Carla [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Foley, Brian [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Leitner, Thomas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Apetrei, Christian [Univ. of Pittsburgh, PA (United States); Hahn, Beatrice [Univ. of Alabama, Tuscaloosa, AL (United States); Mizrachi, Ilene [National Center for Biotechnology Information, Bethesda, MD (United States); Mullins, James [Univ. of Washington, Seattle, WA (United States); Rambaut, Andrew [Univ. of Edinburgh, Scotland (United Kingdom); Wolinsky, Steven [Northwestern Univ., Evanston, IL (United States); Korber, Bette [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
2010-12-31
This compendium is an annual printed summary of the data contained in the HIV sequence database. In these compendia we try to present a judicious selection of the data in such a way that it is of maximum utility to HIV researchers. Each of the alignments attempts to display the genetic variability within the different species, groups and subtypes of the virus. This compendium contains sequences published before January 1, 2010. Hence, though it is called the 2010 Compendium, its contents correspond to the 2009 curated alignments on our website. The number of sequences in the HIV database is still increasing exponentially. In total, at the time of printing, there were 339,306 sequences in the HIV Sequence Database, an increase of 45% since last year. The number of near complete genomes (>7000 nucleotides) increased to 2576 by end of 2009, reflecting a smaller increase than in previous years. However, as in previous years, the compendium alignments contain only a small fraction of these. Included in the alignments are a small number of sequences representing each of the subtypes and the more prevalent circulating recombinant forms (CRFs) such as 01 and 02, as well as a few outgroup sequences (group O and N and SIV-CPZ). Of the rarer CRFs we included one representative each. A more complete version of all alignments is available on our website, http://www.hiv.lanl.gov/content/sequence/NEWALIGN/align.html. Reprints are available from our website in the form of both HTML and PDF files. As always, we are open to complaints and suggestions for improvement. Inquiries and comments regarding the compendium should be addressed to seq-info@lanl.gov.
A P-N Sequence Generator Using LFSR with Dual Edge Trigger Technique
Directory of Open Access Journals (Sweden)
Naghwal Nitin Kumar
2016-01-01
Full Text Available This paper represents the design and implementation of a low power 4-bit LFSR using Dual edge triggered flip flop. A linear feedback shift register (LFSR is assembled by N number of flip flops connected in series and a combinational logic generally xor gate. An LFSR can generate random number sequence which acts as cipher in cryptography. A known text encrypted over long PN sequence, in order to improve security sequence made longer ie 128 bit; require long chain of flip flop leads to more power consumption. In this paper a novel circuit of random sequence generator using dual edge triggered flip flop has been proposed. Data has been generated on every edge of flip flop instead of single edge. A DETFF-LFSR can generate random number require with less number of clock cycle, it minimizes the number of flip flop result in power saving. In this paper we concentrates on the designing of power competent Test Pattern Generator (TPG using four dual edge triggered flip-flops as the basic building block, overall there is reduction of power around 25% by using these techniques.
Energy Technology Data Exchange (ETDEWEB)
Nelson, R.N. (ed.)
1985-05-01
This publication lists all report number codes processed by the Office of Scientific and Technical Information. The report codes are substantially based on the American National Standards Institute, Standard Technical Report Number (STRN)-Format and Creation Z39.23-1983. The Standard Technical Report Number (STRN) provides one of the primary methods of identifying a specific technical report. The STRN consists of two parts: The report code and the sequential number. The report code identifies the issuing organization, a specific program, or a type of document. The sequential number, which is assigned in sequence by each report issuing entity, is not included in this publication. Part I of this compilation is alphabetized by report codes followed by issuing installations. Part II lists the issuing organization followed by the assigned report code(s). In both Parts I and II, the names of issuing organizations appear for the most part in the form used at the time the reports were issued. However, for some of the more prolific installations which have had name changes, all entries have been merged under the current name.
Ergodicity of Random Walks on Random DFA
Balle, Borja
2013-01-01
Given a DFA we consider the random walk that starts at the initial state and at each time step moves to a new state by taking a random transition from the current state. This paper shows that for typical DFA this random walk induces an ergodic Markov chain. The notion of typical DFA is formalized by showing that ergodicity holds with high probability when a DFA is sampled uniformly at random from the set of all automata with a fixed number of states. We also show the same result applies to DF...
Zou, Jian-Jun; Ji, Hong-Jian; Wu, Ding-Wei; Yao, Jing; Hu, Qin; Xiao, Da-Wei; Wang, Guang-Ji
2008-09-01
Meclofenoxate hydrochloride is a psychostimulant in the nootropic agent group available in capsule and tablet formulations approved for traumatic cataphora, alcoholic poisoning, anoxia neonatorum, and children's enuresis in China. Although these 2 generic formulations are marketed in China, information regarding their pharmacokinetics and bioequivalence in humans has not been published. The aim of this study was to compare the pharmacokinetic properties and bioequivalence of the capsule (test) and tablet (reference) formulations of meclofenoxate hydrochloride 200 mg in healthy Chinese volunteers. This single-dose, randomized-sequence, open-label, 2-period crossover study was performed at the Nanjing First Hospital of Nanjing Medical University, Nanjing, China. Eligible subjects were healthy male volunteers who were randomly assigned at a 1:1 ratio to receive a single 200-mg dose of the test or reference formulation, followed by a 1-week washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. As a prodrug, meclofenoxate is hydrolyzed into 4-chlorophenoxyacetic acid and is not detected in plasma. The active metabolite of meclofenoxate, chlorophenoxyacetic acid, was assayed using a high-performance liquid chromatography method. For analysis of pharmacokinetic properties, including Cmax, AUC0-24, and AUC0-infinity, blood samples were obtained at 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 14, and 24 hours after administration. The formulations were considered bioequivalent if the log-transformed ratios of Cmax and AUC were within the predetermined equivalence range (80%-125%) as established by the US Food and Drug Administration (FDA). Subjects were interviewed concerning the occurrence of adverse events including excitement, insomnia, lassitude, and headache. Tolerability was assessed at baseline (before administration) and at 1, 2, 6, and 12 hours after administration by monitoring vital signs
Kim, Bo-Hyung; Kim, Kyu-Pyo; Lim, Kyoung Soo; Kim, Jung-Ryul; Yoon, Seo Hyun; Cho, Joo-Youn; Lee, Yong-Oh; Lee, Kyung-Hee; Jang, In-Jin; Shin, Sang-Goo; Yu, Kyung-Sang
2010-02-01
Ginkgo biloba extract is an herbal medicine used in the treatment of vascular disorders that may be coadministered with antiplatelet agents such as ticlopidine. Regulatory authorities requested evaluation of the pharmacodynamic and pharmacokinetic interactions between these entities, according to the drug-development guidance for fixed-dose combination formulations in Korea. This study was performed to evaluate the potential pharmacodynamic and pharmacokinetic interactions between ticlopidine and Ginkgo biloba extract. An open-label, randomized, 2-period, 2-treatment, 2-sequence, single-dose crossover study was conducted in healthy Korean male volunteers. All volunteers were randomly assigned to a sequence group for the 2 treatments, which consisted of ticlopidine 250 mg alone and ticlopidine 250 mg with Ginkgo biloba extract 80 mg, separated by a 1-week washout period between the treatments. Bleeding time was determined just before dosing and at 5, 12, and 48 hours after dosing. Platelet aggregation was evaluated before dosing and at 4, 8, 26, and 48 hours after dosing. Blood samples (8 mL) from each of the volunteers were collected from an indwelling intravenous cannula inserted into a forearm vein before dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours after dosing. Ticlopidine concentrations were determined by a validated method using HPLC and ultraviolet detection. Adverse events were identified using general health-related questions, vital signs, physical examinations, ECGs, and laboratory tests. A total of 24 healthy men participated in the study (mean [SD] age, 24.1 [4.3] years; weight, 66.6 [7.4] kg; height, 174.7 [5.0] cm). The baseline corrected bleeding times were not significantly different between the ticlopidine-alone and ticlopidine/ Ginkgo biloba groups, and changes in platelet aggregation were not significantly different between the groups. Likewise, the pharmacokinetic parameters of ticlopidine were not significantly different
Liu, Ming-Yan; Wang, Shuang; Yao, Wei-Fan; Wu, Hui-zhe; Meng, Sheng-Nan; Wei, Min-Jie
2009-04-01
Arbidol is an antiviral drug indicated for the prevention and treatment of all types of influenza infection and some other kinds of acute respiratory infections, specifically against influenza groups A and B, and severe acute respiratory syndrome. It is used to help prevent influenza infection as long as necessary with little risk for influenza mutation rendering it less effective. The aim of this study was to compare the pharmacokinetic properties and tolerability, and to determine bioequivalence, of a newly developed generic dispersible tablet formulation (test) and a branded capsule formulation (reference) of arbidol 200 mg in healthy Chinese fasted male volunteers. This open-label, single-dose, randomized-sequence, 2-period crossover study was conducted in healthy native Chinese male volunteers. Eligible subjects were randomly assigned in a 1:1 ratio to receive a single 200-mg dose of the test or reference formulation, followed by a 1-week washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. After the study drug administration, serial blood samples were collected for 72 hours after administration. Plasma drug concentrations were determined using high-performance liquid chromatography coupled with tandem mass spectrometry. Several pharmacokinetic pararameters, including C(max), T(max), t((1/2)), AUC(0-t), and AUC(0-infinity), were determined from the plasma concentrations of the 2 formulations of arbidol using noncompartmental analysis. The formulations were to be considered bioequivalent if the log-transformed ratios of C(max) and AUC were within the predetermined bioequivalence range of 80% to 125% established by the State Food and Drug Administration (SFDA) of the People's Republic of China. Tolerability was assessed by monitoring vital signs (blood pressure, heart rate, temperature, and electrocardiography), laboratory analysis (hematology, blood biochemistry, hepatic function, and
Liu, Yan-Mei; Liu, Yun; Lu, Chuan; Jia, Jing-Ying; Liu, Gang-Yi; Weng, Li-Ping; Wang, Jia-Yan; Li, Guo-Xiu; Wang, Wei; Li, Shui-Jun; Yu, Chen
2010-11-01
Acetylcysteine may be used as a muco- lytic agent for the treatment of chronic bronchitis, chronic obstructive pulmonary disease, and other pulmonary diseases complicated by the production of viscous mucus. However, little is known of its pharmacokinetic properties when given orally in healthy volunteers, particularly in a Chinese Han population. This study was conducted to provide support for the marketing of a generic product in China. The purpose of this study was to compare the pharmacokinetics and relative bioavailability of a generic test formulation and a branded reference formulation of acetylcysteine in fasting healthy Chinese male volunteers. A single-dose, open-label, randomized-sequence, 2-period crossover design with a 7-day washout period between doses was used in this study. Healthy Chinese male nonsmokers aged 18 to 40 years with a body mass index (BMI) of 19 to 25 kg/m(2) were selected. Eligible volunteers were randomly assigned to receive acetylcysteine 600 mg PO as either the test formulation (3 tablets of 200 mg each) or reference formulation (1 tablet of 600 mg) under fasting conditions. A total of 15 serial blood samples were collected over a 24-hour interval, and total plasma acetylcysteine concentrations were analyzed by a validated liquid chromatography-isotopic dilution mass spectrometry method. Pharmacokinetic parameters (C(max), T(max), t(½) AUC(0-t), and AUC(0-∞) were calculated and analyzed statistically. The 2 formulations were considered bioequivalent if the 90% CIs of the log-transformed ratios (test/reference) of C(max) and AUC were within the predetermined bioequivalence ranges (70%-143% for C(max); 80%-125% for AUC), as established by the State Food and Drug Administration of China. Tolerability was determined by vital signs, clinical laboratory tests, 12-lead ECGs, physical examinations, and interviews with the subjects about adverse events (AEs). A total of 24 healthy Chinese Han male volunteers were enrolled in and
Neuhaus, Christine; Eisenberger, Tobias; Decker, Christian; Nagl, Sandra; Blank, Cornelia; Pfister, Markus; Kennerknecht, Ingo; Müller-Hofstede, Cornelie; Charbel Issa, Peter; Heller, Raoul; Beck, Bodo; Rüther, Klaus; Mitter, Diana; Rohrschneider, Klaus; Steinhauer, Ute; Korbmacher, Heike M; Huhle, Dagmar; Elsayed, Solaf M; Taha, Hesham M; Baig, Shahid M; Stöhr, Heidi; Preising, Markus; Markus, Susanne; Moeller, Fabian; Lorenz, Birgit; Nagel-Wolfrum, Kerstin; Khan, Arif O; Bolz, Hanno J
2017-09-01
Combined retinal degeneration and sensorineural hearing impairment is mostly due to autosomal recessive Usher syndrome (USH1: congenital deafness, early retinitis pigmentosa (RP); USH2: progressive hearing impairment, RP). Sanger sequencing and NGS of 112 genes (Usher syndrome, nonsyndromic deafness, overlapping conditions), MLPA, and array-CGH were conducted in 138 patients clinically diagnosed with Usher syndrome. A molecular diagnosis was achieved in 97% of both USH1 and USH2 patients, with biallelic mutations in 97% (USH1) and 90% (USH2), respectively. Quantitative readout reliably detected CNVs (confirmed by MLPA or array-CGH), qualifying targeted NGS as one tool for detecting point mutations and CNVs. CNVs accounted for 10% of identified USH2A alleles, often in trans to seemingly monoallelic point mutations. We demonstrate PTC124-induced read-through of the common p.Trp3955* nonsense mutation (13% of detected USH2A alleles), a potential therapy target. Usher gene mutations were found in most patients with atypical Usher syndrome, but the diagnosis was adjusted in case of double homozygosity for mutations in OTOA and NR2E3, genes implicated in isolated deafness and RP. Two patients with additional enamel dysplasia had biallelic PEX26 mutations, for the first time linking this gene to Heimler syndrome. Targeted NGS not restricted to Usher genes proved beneficial in uncovering conditions mimicking Usher syndrome.
Edgington, Eugene
2007-01-01
Statistical Tests That Do Not Require Random Sampling Randomization Tests Numerical Examples Randomization Tests and Nonrandom Samples The Prevalence of Nonrandom Samples in Experiments The Irrelevance of Random Samples for the Typical Experiment Generalizing from Nonrandom Samples Intelligibility Respect for the Validity of Randomization Tests Versatility Practicality Precursors of Randomization Tests Other Applications of Permutation Tests Questions and Exercises Notes References Randomized Experiments Unique Benefits of Experiments Experimentation without Mani
Repdigits in k-Lucas sequences
Indian Academy of Sciences (India)
57(2) 2000 243-254) proved that 11 is the largest number with only one distinct digit (the so-called repdigit) in the sequence ( L n ( 2 ) ) n . In this paper, we address a similar problem in the family of -Lucas sequences. We also show that the -Lucas sequences have similar properties to those of -Fibonacci sequences ...
Sequence requirement of the ade6-4095 meiotic recombination hotspot in Schizosaccharomyces pombe.
Foulis, Steven J; Fowler, Kyle R; Steiner, Walter W
2018-02-01
Homologous recombination occurs at a greatly elevated frequency in meiosis compared to mitosis and is initiated by programmed double-strand DNA breaks (DSBs). DSBs do not occur at uniform frequency throughout the genome in most organisms, but occur preferentially at a limited number of sites referred to as hotspots. The location of hotspots have been determined at nucleotide-level resolution in both the budding and fission yeasts, and while several patterns have emerged regarding preferred locations for DSB hotspots, it remains unclear why particular sites experience DSBs at much higher frequency than other sites with seemingly similar properties. Short sequence motifs, which are often sites for binding of transcription factors, are known to be responsible for a number of hotspots. In this study we identified the minimum sequence required for activity of one of such motif identified in a screen of random sequences capable of producing recombination hotspots. The experimentally determined sequence, GGTCTRGACC, closely matches the previously inferred sequence. Full hotspot activity requires an effective sequence length of 9.5 bp, whereas moderate activity requires an effective sequence length of approximately 8.2 bp and shows significant association with DSB hotspots. In combination with our previous work, this result is consistent with a large number of different sequence motifs capable of producing recombination hotspots, and supports a model in which hotspots can be rapidly regenerated by mutation as they are lost through recombination.
Graded sets, points and numbers
Herencia González, José Antonio
1998-01-01
The basic tool considered in this paper is the so-called "graded set", defined on the analogy of the family of α-cuts of a fuzzy set. It is also considered the corresponding extensions of the concepts of a point and of a real number (again on the analogy of the fuzzy case). These new "graded concepts" avoid the disadvantages pointed out by Gerla (for the fuzzy points) and by Kaleva and Seikkala (for the convergence of sequences of fuzzy numbers).
Regan, Meredith M.; Neven, Patrick; Giobbie-Hurder, Anita; Goldhirsch, Aron; Ejlertsen, Bent; Mauriac, Louis; Forbes, John F.; Smith, Ian; Láng, István; Wardley, Andrew; Rabaglio, Manuela; Price, Karen N.; Gelber, Richard D.; Coates, Alan S.; Thürlimann, Beat
2011-01-01
clinicaltrials.gov NCT00004205. Findings At a median follow-up of 8.7 years from randomization (range 0–12.4), letrozole monotherapy is significantly better than tamoxifen, whether using IPCW or intention-to-treat (ITT) analysis [IPCW: DFS HR 0.82 (95% CI 0.74–0.92), OS HR 0.79 (0.69–0.900, DRFI HR 0.79 (0.68–0.92), BCFI HR 0.80 (0.70–0.92); ITT: DFS HR 0.86 (0.78–0.96), OS HR 0.87 (0.77–0.999), DRFI HR 0.86 (0.74–0.998), BCFI HR 0.86 (0.76–0.98)]. At a median follow-up of 8.0 years from randomization (range 0–11.2), there were no statistically significant differences in any of the four endpoints for either sequence compared with letrozole monotherapy. Eight-year ITT estimates [each with SE ≤ 1.1%] for letrozole monotherapy, letrozole followed by tamoxifen, and tamoxifen followed by letrozole were 78.6%, 77.8%, 77.3% for DFS; 87.5%, 87.7%, 85.9% for OS; 89.9%, 88.7%, 88.1% for DRFI; and 86.1%, 85.3%, 84.3% for BCFI. Interpretation For postmenopausal women with endocrine-responsive early breast cancer, a reduction in breast cancer recurrence and mortality is obtained by letrozole monotherapy when compared to tamoxifen. Sequential treatments involving tamoxifen and letrozole do not improve outcome compared with letrozole monotherapy, but may represent useful strategies considering individual patient’s risk of recurrence and treatment tolerability: more thromboembolic events, vaginal bleeding, hot flushes and night sweats with tamoxifen, while more vaginal dryness, bone fractures, osteoporosis, arthralgia/myalgia, and higher grade cardiac events with letrozole. Funding Novartis, United States National Cancer Institute, International Breast Cancer Study Group. PMID:22018631
Lifescience Database Archive (English)
Full Text Available Sequences Nucleotide Sequence Nucleotide sequence of full length cDNA (trimmed sequence) kome_ine_full_se...quence_db.fasta.zip kome_ine_full_sequence_db.zip kome_ine_full_sequence_db ...
Sequential selection of random vectors under a sum constraint
Stanke, Mario
2004-01-01
We observe a sequence X1,X2,...,Xn of independent and identically distributed coordinatewise nonnegative d-dimensional random vectors. When a vector is observed it can either be selected or rejected but once made this decision is final. In each coordinate the sum of the selected vectors must not exceed a given constant. The problem is to find a selection policy that maximizes the expected number of selected vectors. For a general absolutely continuous distribution of t...
Directory of Open Access Journals (Sweden)
Haibin Wang
Full Text Available BACKGROUND: Simple sequence repeats (SSRs are ubiquitous in eukaryotic genomes. Chrysanthemum is one of the largest genera in the Asteraceae family. Only few Chrysanthemum expressed sequence tag (EST sequences have been acquired to date, so the number of available EST-SSR markers is very low. METHODOLOGY/PRINCIPAL FINDINGS: Illumina paired-end sequencing technology produced over 53 million sequencing reads from C. nankingense mRNA. The subsequent de novo assembly yielded 70,895 unigenes, of which 45,789 (64.59% unigenes showed similarity to the sequences in NCBI database. Out of 45,789 sequences, 107 have hits to the Chrysanthemum Nr protein database; 679 and 277 sequences have hits to the database of Helianthus and Lactuca species, respectively. MISA software identified a large number of putative EST-SSRs, allowing 1,788 primer pairs to be designed from the de novo transcriptome sequence and a further 363 from archival EST sequence. Among 100 primer pairs randomly chosen, 81 markers have amplicons and 20 are polymorphic for genotypes analysis in Chrysanthemum. The results showed that most (but not all of the assays were transferable across species and that they exposed a significant amount of allelic diversity. CONCLUSIONS/SIGNIFICANCE: SSR markers acquired by transcriptome sequencing are potentially useful for marker-assisted breeding and genetic analysis in the genus Chrysanthemum and its related genera.
Effects of 16S rDNA sampling on estimates of the number of endosymbiont lineages in sucking lice
Directory of Open Access Journals (Sweden)
Julie M. Allen
2016-07-01
Full Text Available Phylogenetic trees can reveal the origins of endosymbiotic lineages of bacteria and detect patterns of co-evolution with their hosts. Although taxon sampling can greatly affect phylogenetic and co-evolutionary inference, most hypotheses of endosymbiont relationships are based on few available bacterial sequences. Here we examined how different sampling strategies of Gammaproteobacteria sequences affect estimates of the number of endosymbiont lineages in parasitic sucking lice (Insecta: Phthirapatera: Anoplura. We estimated the number of louse endosymbiont lineages using both newly obtained and previously sequenced 16S rDNA bacterial sequences and more than 42,000 16S rDNA sequences from other Gammaproteobacteria. We also performed parametric and nonparametric bootstrapping experiments to examine the effects of phylogenetic error and uncertainty on these estimates. Sampling of 16S rDNA sequences affects the estimates of endosymbiont diversity in sucking lice until we reach a threshold of genetic diversity, the size of which depends on the sampling strategy. Sampling by maximizing the diversity of 16S rDNA sequences is more efficient than randomly sampling available 16S rDNA sequences. Although simulation results validate estimates of multiple endosymbiont lineages in sucking lice, the bootstrap results suggest that the precise number of endosymbiont origins is still uncertain.
On Paranorm Zweier -Convergent Sequence Spaces
Directory of Open Access Journals (Sweden)
Vakeel A. Khan
2013-01-01
Full Text Available In this paper, we introduce the paranorm Zweier -convergent sequence spaces , , and , a sequence of positive real numbers. We study some topological properties, prove the decomposition theorem, and study some inclusion relations on these spaces.
Zhang, Yuan-Yuan; Liu, Jun-Hong; Su, Feng; Lui, Ying-Tao; Li, Jun-Feng
2009-04-01
Iron deficiency anemia (IDA) is a common nutritional disease worldwide. Iron supplementation is an efficient method for treating patients with IDA. Polysaccharide iron complex is an oral iron supplement that is associated with generally good tolerability and good bioavailability. The aim of this study was to evaluate the bioequivalence of 2 branded formulations of polysaccharide iron complex in healthy adult male Chinese volunteers by determining the pharmacokinetic parameters after single-dose oral admi ni strati on. This sequence-randomized, double-blind, 2-way crossover study was carried out in the Affiliated Hospital, Institute of Medical Sciences of Qingdao University, Qingdao, China. Healthy adult male Chinese volunteers were enrolled and evenly randomized to receive 1 of 2 formulations on day 1. Subjects received an oral dose of 150 mg (1 capsule) of polysaccharide iron complex with 150 mL of warm water in the morning. Capsules were of similar size, shape, and color to ensure blinding. Four hours after administration, the subjects were given standardized meals. After a 1-week washout period, the subjects were crossed over to receive the other formulation in a similar manner. The serum iron concentration 12 hours after study drug administration was determined using atomic-absorption spectrometry. The pharmacokinetic parameters Cmax, Tmax, AUC0-t, and AUC0-∞ were obtained and analyzed using the Schuir mann 2 one-sided t test. The 2 formulations were considered bioequi valent if the test/reference ratios of Cmax, AUC0-t, and their 90% CIs were within the range of 70% to 143% for Cmax and within 80% to 125% for AUC0-t. Tolerability was monitored by inquiring whether the subjects had experienced adverse events (AEs), with a focus on gastrointestinal AEs, during the clinic visits during the 24-hour period after drag administration and subsequently via telephone throughout the study. Thirty adult male Chinese volunteers were assessed for inclusion. Twenty healthy
Jiang, Tao; Rong, Zhengxing; Xu, Yiping; Chen, Bing; Xie, Yifan; Chen, Congying; Lu, Yang; Shen, Yifeng; Li, Huafang; Sun, Jing; Chen, Hongzhuan
2013-01-01
Citalopram is a selective serotonin reuptake inhibitor (SSRI) mainly prescribed to treat major depression. The aim of this study was to compare the pharmacokinetic characteristics of a new and a branded citalopram 20 mg formulation to support the marketing authorization of the test formulation in China. A single-dose, open-label, randomized-sequence, two-period crossover design was used in this study. Healthy Chinese male cytochrome P450 (CYP) 2C19 extensive metabolizers, aged 18-40 years, were eligible to participate. CYP2C19 poor metabolizers were excluded, based on genotyping of genomic DNA from blood samples. Twenty-four subjects were randomly assigned to receive the test formulation followed by the reference formulation, and then vice versa. A 2-week washout occurred between study periods. Blood samples were collected for up to 144 h post-dose. Quantification was carried out using a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. Pharmacokinetic parameters were calculated and analysed statistically. The two formulations were considered pharmacokinetically equivalent if the 90 % confidence intervals (CIs) of the log-transformed ratios (test/reference) of the maximum plasma concentration (C(max)), area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC(last)), and area under the plasma concentration-time curve from time zero to infinity (AUC(∞)) were within the predetermined acceptance range (70-143 % for C(max); 80-125 % for AUC(last) and AUC(∞)) according to China State Food and Drug Administration bioequivalence guidelines. Tolerability was monitored by clinical assessment, vital signs, laboratory analysis and interviews with participants about adverse events. A total of 24 participants, with a mean (SD) age of 26 (3) years (range 22-32 years), body weight of 65.2 (5.0) kg (range 53-73 kg), and height of 172.7 (4.9) cm (range 159-182 cm), were enrolled in this
Choi, YoonJung; Lee, SeungHwan; Cho, Sang-Min; Kang, Won-Ho; Nam, Kyu-Yeol; Jang, In-Jin; Yu, Kyung-Sang
2016-01-01
A fixed-dose combination (FDC) of amlodipine and losartan has been used to reduce blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The aim of this study was to evaluate the pharmacokinetic (PK) characteristics and tolerability of an FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium compared to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium in healthy subjects. A randomized, open-label, single-dose, two-period, two-sequence crossover study was conducted on 46 healthy male subjects. Blood concentrations were measured by liquid chromatography-tandem mass spectrometry. Blood samples were collected up to 144 hours post dose for each period. PK parameters were calculated in each treatment group using a noncompartmental method. The 90% confidence intervals (CIs) of the geometric mean ratios of the two treatments for the maximum plasma concentration (Cmax) and the area under the concentration curve from time zero to the last quantifiable time point (AUC0-t) were estimated. Tolerability assessments were performed for all subjects who received the drug at least once. The PK profiles of the two treatments were similar. For amlodipine, the geometric mean ratios (90% CIs) of amlodipine besylate to amlodipine camsylate for the Cmax and AUC0-t were 0.98 (0.94-1.01) and 0.97 (0.93-1.01), respectively. The corresponding values for losartan were 0.91 (0.81-1.02) and 1.05 (0.98-1.12), respectively. The incidence of adverse events was not significantly different between the two treatments, and both were well tolerated. An FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium produced similar results to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium treatment with respect to the PK parameters of amlodipine and losartan based on Cmax and AUC0-t values. The amlodipine besylate/losartan potassium combination was well tolerated by healthy male subjects.
Grimshaw, Jeremy M; Presseau, Justin; Tetroe, Jacqueline; Eccles, Martin P; Francis, Jill J; Godin, Gaston; Graham, Ian D; Hux, Janet E; Johnston, Marie; Légaré, France; Lemyre, Louise; Robinson, Nicole; Zwarenstein, Merrick
2014-08-06
Theory-based process evaluations conducted alongside randomized controlled trials provide the opportunity to investigate hypothesized mechanisms of action of interventions, helping to build a cumulative knowledge base and to inform the interpretation of individual trial outcomes. Our objective was to identify the underlying causal mechanisms in a cluster randomized trial of the effectiveness of printed educational materials (PEMs) to increase referral for diabetic retinopathy screening. We hypothesized that the PEMs would increase physicians' intention to refer patients for retinal screening by strengthening their attitude and subjective norm, but not their perceived behavioral control. Design: A theory based process evaluation alongside the Ontario Printed Educational Material (OPEM) cluster randomized trial. Postal surveys based on the Theory of Planned Behavior were sent to a random sample of trial participants two months before and six months after they received the intervention. Setting: Family physicians in Ontario, Canada. Participants: 1,512 family physicians (252 per intervention group) from the OPEM trial were invited to participate, and 31.3% (473/1512) responded at time one and time two. The final sample comprised 437 family physicians fully completing questionnaires at both time points. Main Outcome Measures: Primary: behavioral intention related to referring patient for retinopathy screening; secondary: attitude, subjective norm, perceived behavioral control. At baseline, family physicians reported positive intention, attitude, subjective norm, and perceived behavioral control to advise patients about retinopathy screening suggesting limited opportunities for improvement in these constructs. There were no significant differences on intention, attitude, subjective norm, and perceived behavioral control following the intervention. Respondents also reported additional physician- and patient-related factors perceived to influence whether patients received
Chunking in task sequences modulates task inhibition.
Koch, Iring; Philipp, Andrea M; Gade, Miriam
2006-04-01
In a study of the formation of representations of task sequences and its influence on task inhibition, participants first performed tasks in a predictable sequence (e.g., ABACBC) and then performed the tasks in a random sequence. Half of the participants were explicitly instructed about the predictable sequence, whereas the other participants did not receive these instructions. Task-sequence learning was inferred from shorter reaction times (RTs) in predictable relative to random sequences. Persisting inhibition of competing tasks was indicated by increased RTs in n- 2 task repetitions (e.g., ABA) compared with n- 2 nonrepetitions (e.g., CBA). The results show task-sequence learning for both groups. However, task inhibition was reduced in predictable relative to random sequences among instructed-learning participants who formed an explicit representation of the task sequence, whereas sequence learning and task inhibition were independent in the noninstructed group. We hypothesize that the explicit instructions led to chunking of the task sequence, and that n- 2 repetitions served as chunk points (ABA-CBC), so that within-chunk facilitation modulated the inhibition effect.