Semenova, E.V.; Jore, M.M.; Westra, E.R.; Oost, van der J.; Brouns, S.J.J.
2011-01-01
Prokaryotic clustered regularly interspaced short palindromic repeat (CRISPR)/Cas (CRISPR-associated sequences) systems provide adaptive immunity against viruses when a spacer sequence of small CRISPR RNA (crRNA) matches a protospacer sequence in the viral genome. Viruses that escape CRISPR/Cas
CTD2 researchers at the University of California in San Francisco developed a modified Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) CRISPR/dCas9 system. Catalytically inactive dCas9 enables modular and programmable RNA-guided genome regulation in eukaryotes.
Cui, Yujun; Li, Yanjun; Yan, Yanfeng; Yang, Ruifu
2008-11-01
CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats), the basis of spoligotyping technology, can provide prokaryotes with heritable adaptive immunity against phages' invasion. Studies on CRISPR loci and their associated elements, including various CAS (CRISPR-associated) proteins and leader sequences, are still in its infant period. We introduce the brief history', structure, function, bioinformatics research and application of this amazing immunity system in prokaryotic organism for inspiring more scientists to find their interest in this developing topic.
Al-Attar, S.; Westra, E.R.; Oost, van der J.; Brouns, S.J.J.
2011-01-01
Many prokaryotes contain the recently discovered defense system against mobile genetic elements. This defense system contains a unique type of repetitive DNA stretches, termed Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs). CRISPRs consist of identical repeated DNA sequences
He, Jiankui; Deem, Michael W.
2010-09-01
Clustered regularly interspaced short palindromic repeats (CRISPR) in bacterial and archaeal DNA have recently been shown to be a new type of antiviral immune system in these organisms. We here study the diversity of spacers in CRISPR under selective pressure. We propose a population dynamics model that explains the biological observation that the leader-proximal end of CRISPR is more diversified and the leader-distal end of CRISPR is more conserved. This result is shown to be in agreement with recent experiments. Our results show that the CRISPR spacer structure is influenced by and provides a record of the viral challenges that bacteria face.
Wang, Pengfei; Wang, Yingfang; Duan, Guangcai; Xue, Zerun; Wang, Linlin; Guo, Xiangjiao; Yang, Haiyan; Xi, Yuanlin
2015-04-01
This study was aimed to explore the features of clustered regularly interspaced short palindromic repeats (CRISPR) structures in Shigella by using bioinformatics. We used bioinformatics methods, including BLAST, alignment and RNA structure prediction, to analyze the CRISPR structures of Shigella genomes. The results showed that the CRISPRs existed in the four groups of Shigella, and the flanking sequences of upstream CRISPRs could be classified into the same group with those of the downstream. We also found some relatively conserved palindromic motifs in the leader sequences. Repeat sequences had the same group with corresponding flanking sequences, and could be classified into two different types by their RNA secondary structures, which contain "stem" and "ring". Some spacers were found to homologize with part sequences of plasmids or phages. The study indicated that there were correlations between repeat sequences and flanking sequences, and the repeats might act as a kind of recognition mechanism to mediate the interaction between foreign genetic elements and Cas proteins.
Li, Hao; Qiu, Shaofu; Song, Hongbin
2013-10-04
In survival competition with phage, bacteria and archaea gradually evolved the acquired immune system--Clustered regularly interspaced short palindromic repeats (CRISPR), presenting the trait of transcribing the crRNA and the CRISPR-associated protein (Cas) to silence or cleaving the foreign double-stranded DNA specifically. In recent years, strong interest arises in prokaryotes primitive immune system and many in-depth researches are going on. Recently, researchers successfully repurposed CRISPR as an RNA-guided platform for sequence-specific gene expression, which provides a simple approach for selectively perturbing gene expression on a genome-wide scale. It will undoubtedly bring genome engineering into a more convenient and accurate new era.
[Clustered regularly interspaced short palindromic repeats (CRISPR) site in Bacillus anthracis].
Gao, Zhiqi; Wang, Dongshu; Feng, Erling; Wang, Bingxiang; Hui, Yiming; Han, Shaobo; Jiao, Lei; Liu, Xiankai; Wang, Hengliang
2014-11-04
To investigate the polymorphism of clustered regularly interspaced short palindromic repeats (CRISPR) in Bacillu santhracis and the application to molecular typing based on the polymorphism of CRISPR in B. anthracis. We downloaded the whole genome sequence of 6 B. anthracis strains and extracted the CRISPR sites. We designed the primers of CRISPR sites and amplified the CRISPR fragments in 193 B. anthracis strains by PCR and sequenced these fragments. In order to reveal the polymorphism of CRISPR in B. anthracis, wealigned all the extracted sequences and sequenced results by local blasting. At the same time, we also analyzed the CRISPR sites in B. cereus and B. thuringiensis. We did not find any polymorphism of CRISPR in B. anthracis. The molecular typing approach based on CRISPR polymorphism is not suitable for B. anthracis, but it is possible for us to distinguish B. anthracis from B. cereus and B. thuringiensis.
Guo, Lijun; Xu, Kun; Liu, Zhiyuan; Zhang, Cunfang; Xin, Ying; Zhang, Zhiying
2015-06-01
In addition to the advantages of scalable, affordable, and easy to engineer, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) technology is superior for multiplex targeting, which is laborious and inconvenient when achieved by cloning multiple gRNA expressing cassettes. Here, we report a simple CRISPR array assembling method which will facilitate multiplex targeting usage. First, the Streptococcus thermophilus CRISPR3/Cas locus was cloned. Second, different CRISPR arrays were assembled with different crRNA spacers. Transformation assays using different Escherichia coli strains demonstrated efficient plasmid DNA targeting, and we achieved targeting efficiency up to 95% with an assembled CRISPR array with three crRNA spacers. Copyright © 2015 Elsevier Inc. All rights reserved.
Directory of Open Access Journals (Sweden)
Peter C. Fineran
2012-10-01
Full Text Available Phages are the most abundant biological entities on earth and pose a constant challenge to their bacterial hosts. Thus, bacteria have evolved numerous ‘innate’ mechanisms of defense against phage, such as abortive infection or restriction/modification systems. In contrast, the clustered regularly interspaced short palindromic repeats (CRISPR systems provide acquired, yet heritable, sequence-specific ‘adaptive’ immunity against phage and other horizontally-acquired elements, such as plasmids. Resistance is acquired following viral infection or plasmid uptake when a short sequence of the foreign genome is added to the CRISPR array. CRISPRs are then transcribed and processed, generally by CRISPR associated (Cas proteins, into short interfering RNAs (crRNAs, which form part of a ribonucleoprotein complex. This complex guides the crRNA to the complementary invading nucleic acid and targets this for degradation. Recently, there have been rapid advances in our understanding of CRISPR/Cas systems. In this review, we will present the current model(s of the molecular events involved in both the acquisition of immunity and interference stages and will also address recent progress in our knowledge of the regulation of CRISPR/Cas systems.
Briner, Alexandra E; Barrangou, Rodolphe
2014-02-01
Clustered regularly interspaced short palindromic repeats (CRISPR) in combination with associated sequences (cas) constitute the CRISPR-Cas immune system, which uptakes DNA from invasive genetic elements as novel "spacers" that provide a genetic record of immunization events. We investigated the potential of CRISPR-based genotyping of Lactobacillus buchneri, a species relevant for commercial silage, bioethanol, and vegetable fermentations. Upon investigating the occurrence and diversity of CRISPR-Cas systems in Lactobacillus buchneri genomes, we observed a ubiquitous occurrence of CRISPR arrays containing a 36-nucleotide (nt) type II-A CRISPR locus adjacent to four cas genes, including the universal cas1 and cas2 genes and the type II signature gene cas9. Comparative analysis of CRISPR spacer content in 26 L. buchneri pickle fermentation isolates associated with spoilage revealed 10 unique locus genotypes that contained between 9 and 29 variable spacers. We observed a set of conserved spacers at the ancestral end, reflecting a common origin, as well as leader-end polymorphisms, reflecting recent divergence. Some of these spacers showed perfect identity with phage sequences, and many spacers showed homology to Lactobacillus plasmid sequences. Following a comparative analysis of sequences immediately flanking protospacers that matched CRISPR spacers, we identified a novel putative protospacer-adjacent motif (PAM), 5'-AAAA-3'. Overall, these findings suggest that type II-A CRISPR-Cas systems are valuable for genotyping of L. buchneri.
Richter, Corinna; Chang, James T; Fineran, Peter C
2012-10-19
Phages are the most abundant biological entities on earth and pose a constant challenge to their bacterial hosts. Thus, bacteria have evolved numerous 'innate' mechanisms of defense against phage, such as abortive infection or restriction/modification systems. In contrast, the clustered regularly interspaced short palindromic repeats (CRISPR) systems provide acquired, yet heritable, sequence-specific 'adaptive' immunity against phage and other horizontally-acquired elements, such as plasmids. Resistance is acquired following viral infection or plasmid uptake when a short sequence of the foreign genome is added to the CRISPR array. CRISPRs are then transcribed and processed, generally by CRISPR associated (Cas) proteins, into short interfering RNAs (crRNAs), which form part of a ribonucleoprotein complex. This complex guides the crRNA to the complementary invading nucleic acid and targets this for degradation. Recently, there have been rapid advances in our understanding of CRISPR/Cas systems. In this review, we will present the current model(s) of the molecular events involved in both the acquisition of immunity and interference stages and will also address recent progress in our knowledge of the regulation of CRISPR/Cas systems.
[Molecular characteristics of Clustered Regularly Interspaced Short Palindromic Repeat in Shigella].
Xue, Zerun; Wang, Yingfang; Duan, Guangcai; Yang, Haiyan; Xi, Yuanlin; Wang, Pengfei; Wang, Linlin; Guo, Xiangjiao
2015-08-01
To detect the molecular characteristics of Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) in Shigella and to analyze the distribution of CRISPR related to the time of isolation. Of the 52 Shigella strains, 41 were isolated from Henan, 6 from Jiangxi and 5 isolated from Beijing. Both CRISPR locus of S1, S2, S3 and S4 in Shigella were detected by polymerase chain reaction (PCR). The PCR products were sequenced and compared. The positive rates of CRISPR locus in Shigella were 33.69% (S1), 50.00% (S2), 82.69% (S3) and 73.08% (S4), respectively. Two subtypes were discovered in S1 and S3 locus. Three subtypes were discovered in S2 locus. Four different subtypes were discovered in S4 locus. The isolates from Henan strains were divided into two groups by the time of isolation. Distributions of S1 were different, before or after 2004, on Shigella. S1 could not be detected after 2004. There were no statistical differences of S2, S3 and S4 in two groups. Different CRISPR subtypes or Shigella were discovered. A significant correlation was noticed between the CRISPR S1 related to the time of isolation but not between S2, S3 or S4 on the time of isolation.
Fu, Qiang; Su, Zhixin; Cheng, Yuqiang; Wang, Zhaofei; Li, Shiyu; Wang, Heng'an; Sun, Jianhe; Yan, Yaxian
In order to investigate the diverse characteristics of clustered, regularly interspaced short palindromic repeat (CRISPR) arrays and the distribution of virulence factor genes in avian Escherichia coli, 80 E. coli isolates obtained from chickens with avian pathogenic E. coli (APEC) or avian fecal commensal E. coli (AFEC) were identified. Using the multiplex polymerase chain reaction (PCR), five genes were subjected to phylogenetic typing and examined for CRISPR arrays to study genetic relatedness among the strains. The strains were further analyzed for CRISPR loci and virulence factor genes to determine a possible association between their CRISPR elements and their potential virulence. The strains were divided into five phylogenetic groups: A, B1, B2, D and E. It was confirmed that two types of CRISPR arrays, CRISPR1 and CRISPR2, which contain up to 246 distinct spacers, were amplified in most of the strains. Further classification of the isolates was achieved by sorting them into nine CRISPR clusters based on their spacer profiles, which indicates a candidate typing method for E. coli. Several significant differences in invasion-associated gene distribution were found between the APEC isolates and the AFEC isolates. Our results identified the distribution of 11 virulence genes and CRISPR diversity in 80 strains. It was demonstrated that, with the exception of iucD and aslA, there was no sharp demarcation in the gene distribution between the pathogenic (APEC) and commensal (AFEC) strains, while the total number of indicated CRISPR spacers may have a positive correlation with the potential pathogenicity of the E. coli isolates. Copyright © 2016. Published by Elsevier Masson SAS.
Directory of Open Access Journals (Sweden)
Yujun Cui
Full Text Available BACKGROUND: Yersinia pestis, the pathogen of plague, has greatly influenced human history on a global scale. Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR, an element participating in immunity against phages' invasion, is composed of short repeated sequences separated by unique spacers and provides the basis of the spoligotyping technology. In the present research, three CRISPR loci were analyzed in 125 strains of Y. pestis from 26 natural plague foci of China, the former Soviet Union and Mongolia were analyzed, for validating CRISPR-based genotyping method and better understanding adaptive microevolution of Y. pestis. METHODOLOGY/PRINCIPAL FINDINGS: Using PCR amplification, sequencing and online data processing, a high degree of genetic diversity was revealed in all three CRISPR elements. The distribution of spacers and their arrays in Y. pestis strains is strongly region and focus-specific, allowing the construction of a hypothetic evolutionary model of Y. pestis. This model suggests transmission route of microtus strains that encircled Takla Makan Desert and ZhunGer Basin. Starting from Tadjikistan, one branch passed through the Kunlun Mountains, and moved to the Qinghai-Tibet Plateau. Another branch went north via the Pamirs Plateau, the Tianshan Mountains, the Altai Mountains and the Inner Mongolian Plateau. Other Y. pestis lineages might be originated from certain areas along those routes. CONCLUSIONS/SIGNIFICANCE: CRISPR can provide important information for genotyping and evolutionary research of bacteria, which will help to trace the source of outbreaks. The resulting data will make possible the development of very low cost and high-resolution assays for the systematic typing of any new isolate.
Zhang, Fan; Zhang, Bing; Xiang, Hua; Hu, Songnian
2009-11-01
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) is a widespread system that provides acquired resistance against phages in bacteria and archaea. Here we aim to genome-widely analyze the CRISPR in extreme halophilic archaea, of which the whole genome sequences are available at present time. We used bioinformatics methods including alignment, conservation analysis, GC content and RNA structure prediction to analyze the CRISPR structures of 7 haloarchaeal genomes. We identified the CRISPR structures in 5 halophilic archaea and revealed a conserved palindromic motif in the flanking regions of these CRISPR structures. In addition, we found that the repeat sequences of large CRISPR structures in halophilic archaea were greatly conserved, and two types of predicted RNA secondary structures derived from the repeat sequences were likely determined by the fourth base of the repeat sequence. Our results support the proposal that the leader sequence may function as recognition site by having palindromic structures in flanking regions, and the stem-loop secondary structure formed by repeat sequences may function in mediating the interaction between foreign genetic elements and CAS-encoded proteins.
Sun, S J; Huo, J H; Geng, Z J; Sun, X Y; Fu, X B
2018-04-20
Gene engineering has attracted worldwide attention because of its ability of precise location of disease mutations in genome. As a new gene editing technology, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system is simple, fast, and accurate to operate at a specific gene site. It overcomes the long-standing problem of conventional operation. At the same time, stem cells are a good foundation for establishing disease model in vitro. Therefore, it has great significance to combine stem cells with the rapidly developing gene manipulation techniques. In this review, we mainly focus on the mechanism of CRISPR/Cas9 technology and its application in stem cell genomic editing, so as to pave the way for promoting rapid application and development of CRISPR/Cas9 technology.
Al-Attar, Sinan; Westra, Edze R; van der Oost, John; Brouns, Stan J J
2011-04-01
Many prokaryotes contain the recently discovered defense system against mobile genetic elements. This defense system contains a unique type of repetitive DNA stretches, termed Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs). CRISPRs consist of identical repeated DNA sequences (repeats), interspaced by highly variable sequences referred to as spacers. The spacers originate from either phages or plasmids and comprise the prokaryotes' 'immunological memory'. CRISPR-associated (cas) genes encode conserved proteins that together with CRISPRs make-up the CRISPR/Cas system, responsible for defending the prokaryotic cell against invaders. CRISPR-mediated resistance has been proposed to involve three stages: (i) CRISPR-Adaptation, the invader DNA is encountered by the CRISPR/Cas machinery and an invader-derived short DNA fragment is incorporated in the CRISPR array. (ii) CRISPR-Expression, the CRISPR array is transcribed and the transcript is processed by Cas proteins. (iii) CRISPR-Interference, the invaders' nucleic acid is recognized by complementarity to the crRNA and neutralized. An application of the CRISPR/Cas system is the immunization of industry-relevant prokaryotes (or eukaryotes) against mobile-genetic invasion. In addition, the high variability of the CRISPR spacer content can be exploited for phylogenetic and evolutionary studies. Despite impressive progress during the last couple of years, the elucidation of several fundamental details will be a major challenge in future research.
Stachler, Aris-Edda; Marchfelder, Anita
2016-07-15
The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system is used by bacteria and archaea to fend off foreign genetic elements. Since its discovery it has been developed into numerous applications like genome editing and regulation of transcription in eukaryotes and bacteria. For archaea currently no tools for transcriptional repression exist. Because molecular biology analyses in archaea become more and more widespread such a tool is vital for investigating the biological function of essential genes in archaea. Here we use the model archaeon Haloferax volcanii to demonstrate that its endogenous CRISPR-Cas system I-B can be harnessed to repress gene expression in archaea. Deletion of cas3 and cas6b genes results in efficient repression of transcription. crRNAs targeting the promoter region reduced transcript levels down to 8%. crRNAs targeting the reading frame have only slight impact on transcription. crRNAs that target the coding strand repress expression only down to 88%, whereas crRNAs targeting the template strand repress expression down to 8%. Repression of an essential gene results in reduction of transcription levels down to 22%. Targeting efficiencies can be enhanced by expressing a catalytically inactive Cas3 mutant. Genes can be targeted on plasmids or on the chromosome, they can be monocistronic or part of a polycistronic operon. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Beloglazova, Natalia; Brown, Greg; Zimmerman, Matthew D; Proudfoot, Michael; Makarova, Kira S; Kudritska, Marina; Kochinyan, Samvel; Wang, Shuren; Chruszcz, Maksymilian; Minor, Wladek; Koonin, Eugene V; Edwards, Aled M; Savchenko, Alexei; Yakunin, Alexander F
2008-07-18
Clustered regularly interspaced short palindromic repeats (CRISPRs) together with the associated CAS proteins protect microbial cells from invasion by foreign genetic elements using presently unknown molecular mechanisms. All CRISPR systems contain proteins of the CAS2 family, suggesting that these uncharacterized proteins play a central role in this process. Here we show that the CAS2 proteins represent a novel family of endoribonucleases. Six purified CAS2 proteins from diverse organisms cleaved single-stranded RNAs preferentially within U-rich regions. A representative CAS2 enzyme, SSO1404 from Sulfolobus solfataricus, cleaved the phosphodiester linkage on the 3'-side and generated 5'-phosphate- and 3'-hydroxyl-terminated oligonucleotides. The crystal structure of SSO1404 was solved at 1.6A resolution revealing the first ribonuclease with a ferredoxin-like fold. Mutagenesis of SSO1404 identified six residues (Tyr-9, Asp-10, Arg-17, Arg-19, Arg-31, and Phe-37) that are important for enzymatic activity and suggested that Asp-10 might be the principal catalytic residue. Thus, CAS2 proteins are sequence-specific endoribonucleases, and we propose that their role in the CRISPR-mediated anti-phage defense might involve degradation of phage or cellular mRNAs.
Rezzonico, Fabio; Smits, Theo H M; Duffy, Brion
2011-06-01
The clustered regularly interspaced short palindromic repeat (CRISPR)/Cas system confers acquired heritable immunity against mobile nucleic acid elements in prokaryotes, limiting phage infection and horizontal gene transfer of plasmids. In CRISPR arrays, characteristic repeats are interspersed with similarly sized nonrepetitive spacers derived from transmissible genetic elements and acquired when the cell is challenged with foreign DNA. New spacers are added sequentially and the number and type of CRISPR units can differ among strains, providing a record of phage/plasmid exposure within a species and giving a valuable typing tool. The aim of this work was to investigate CRISPR diversity in the highly homogeneous species Erwinia amylovora, the causal agent of fire blight. A total of 18 CRISPR genotypes were defined within a collection of 37 cosmopolitan strains. Strains from Spiraeoideae plants clustered in three major groups: groups II and III were composed exclusively of bacteria originating from the United States, whereas group I generally contained strains of more recent dissemination obtained in Europe, New Zealand, and the Middle East. Strains from Rosoideae and Indian hawthorn (Rhaphiolepis indica) clustered separately and displayed a higher intrinsic diversity than that of isolates from Spiraeoideae plants. Reciprocal exclusion was generally observed between plasmid content and cognate spacer sequences, supporting the role of the CRISPR/Cas system in protecting against foreign DNA elements. However, in several group III strains, retention of plasmid pEU30 is inconsistent with a functional CRISPR/Cas system.
Zheng, Po-Xing; Chan, Yuen-Chi; Chiou, Chien-Shun; Chiang-Ni, Chuan; Wang, Shu-Ying; Tsai, Pei-Jane; Chuang, Woei-Jer; Lin, Yee-Shin; Liu, Ching-Chuan; Wu, Jiunn-Jong
2015-01-01
Clustered regularly interspaced short palindromic repeats (CRISPR) are the bacterial adaptive immune system against foreign nucleic acids. Given the variable nature of CRISPR, it could be a good marker for molecular epidemiology. Group A streptococcus is one of the major human pathogens. It has two CRISPR loci, including CRISPR01 and CRISPR02. The aim of this study was to analyze the distribution of CRISPR-associated gene cassettes (cas) and CRISPR arrays in highly prevalent emm types. The cas cassette and CRISPR array in two CRISPR loci were analyzed in a total of 332 strains, including emm1, emm3, emm4, emm12, and emm28 strains. The CRISPR type was defined by the spacer content of each CRISPR array. All strains had at least one cas cassette or CRISPR array. More than 90% of the spacers were found in one emm type, specifically. Comparing the consistency between emm and CRISPR types by Simpson's index of diversity and the adjusted Wallace coefficient, CRISPR01 type was concordant to emm type, and CRISPR02 showed unidirectional congruence to emm type, suggesting that at least for the majority of isolates causing infection in high income countries, the emm type can be inferred from CRISPR analysis, which can further discriminate isolates sharing the same emm type.
Pride, David T; Salzman, Julia; Relman, David A
2012-09-01
Explorations of human microbiota have provided substantial insight into microbial community composition; however, little is known about interactions between various microbial components in human ecosystems. In response to the powerful impact of viral predation, bacteria have acquired potent defences, including an adaptive immune response based on the clustered regularly interspaced short palindromic repeats (CRISPRs)/Cas system. To improve our understanding of the interactions between bacteria and their viruses in humans, we analysed 13 977 streptococcal CRISPR sequences and compared them with 2 588 172 virome reads in the saliva of four human subjects over 17 months. We found a diverse array of viruses and CRISPR spacers, many of which were specific to each subject and time point. There were numerous viral sequences matching CRISPR spacers; these matches were highly specific for salivary viruses. We determined that spacers and viruses coexist at the same time, which suggests that streptococcal CRISPR/Cas systems are under constant pressure from salivary viruses. CRISPRs in some subjects were just as likely to match viral sequences from other subjects as they were to match viruses from the same subject. Because interactions between bacteria and viruses help to determine the structure of bacterial communities, CRISPR-virus analyses are likely to provide insight into the forces shaping the human microbiome. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.
Hara, Yasushi; Hayashi, Kyohei; Nakajima, Takuya; Kagawa, Shizuko; Tazumi, Akihiro; Moore, John E; Matsuda, Motoo
2013-09-01
Clustered regularly interspaced short palindromic repeats (CRISPRs), of approximately 10,000 base pairs (bp) in length, were shown to occur in the Japanese Taylorella equigenitalis strain, EQ59. The locus was composed of the putative CRISPRs-associated with 5 (cas5), RAMP csd1, csd2, recB, cas1, a leader region, 13 CRISPR consensus sequence repeats (each 32 bp; 5'-TCAGCCACGTTCGCGTGGCTGTGTGTTTAAAG-3'). These were in turn separated by 12 non repetitive unique spacer regions of similar length. In addition, a leader region, a transposase/IS protein, a leader region, and cas3 were also seen. All seven putative open reading frames carry their ribosome binding sites. Promoter consensus sequences at the -35 and -10 regions and putative intrinsic ρ-independent transcription terminator regions also occurred. A possible long overlap of 170 bp in length occurred between the recB and cas1 loci. Positive reverse transcription PCR signals of cas5, RAMP csd1, csd2-recB/cas1, and cas3 were generated. A putative secondary structure of the CRISPR consensus repeats was constructed. Following this, CRISPR results of the T. equigenitalis EQ59 isolate were subsequently compared with those from the Taylorella asinigenitalis MCE3 isolate.
Stachler, Aris-Edda; Marchfelder, Anita
2016-01-01
The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system is used by bacteria and archaea to fend off foreign genetic elements. Since its discovery it has been developed into numerous applications like genome editing and regulation of transcription in eukaryotes and bacteria. For archaea currently no tools for transcriptional repression exist. Because molecular biology analyses in archaea become more and more widespread such a tool is vital for investigating the biological function of essential genes in archaea. Here we use the model archaeon Haloferax volcanii to demonstrate that its endogenous CRISPR-Cas system I-B can be harnessed to repress gene expression in archaea. Deletion of cas3 and cas6b genes results in efficient repression of transcription. crRNAs targeting the promoter region reduced transcript levels down to 8%. crRNAs targeting the reading frame have only slight impact on transcription. crRNAs that target the coding strand repress expression only down to 88%, whereas crRNAs targeting the template strand repress expression down to 8%. Repression of an essential gene results in reduction of transcription levels down to 22%. Targeting efficiencies can be enhanced by expressing a catalytically inactive Cas3 mutant. Genes can be targeted on plasmids or on the chromosome, they can be monocistronic or part of a polycistronic operon. PMID:27226589
Burmistrz, Michal; Rodriguez Martinez, Jose Ignacio; Krochmal, Daniel; Staniec, Dominika; Pyrc, Krzysztof
2017-12-01
The CRISPR-Cas (clustered regularly interspaced short palindromic repeat-CRISPR-associated protein) system is unique to prokaryotes and provides the majority of bacteria and archaea with immunity against nucleic acids of foreign origin. CRISPR RNAs (crRNAs) are the key element of this system, since they are responsible for its selectivity and effectiveness. Typical crRNAs consist of a spacer sequence flanked with 5' and 3' handles originating from repeat sequences that are important for recognition of these small RNAs by the Cas machinery. In this investigation, we studied the type I-C CRISPR-Cas system in Porphyromonas gingivalis , a human pathogen associated with periodontitis, rheumatoid arthritis, cardiovascular disease, and aspiration pneumonia. We demonstrated the importance of the 5' handle for crRNA recognition by the effector complex and consequently activity, as well as secondary trimming of the 3' handle, which was not affected by modifications of the repeat sequence. IMPORTANCE Porphyromonas gingivalis , a clinically relevant Gram-negative, anaerobic bacterium, is one of the major etiologic agents of periodontitis and has been linked with the development of other clinical conditions, including rheumatoid arthritis, cardiovascular disease, and aspiration pneumonia. The presented results on the biogenesis and functions of crRNAs expand our understanding of CRISPR-Cas cellular defenses in P. gingivalis and of horizontal gene transfer in bacteria. Copyright © 2017 American Society for Microbiology.
Nam, Ki Hyun; Ding, Fran; Haitjema, Charles; Huang, Qingqiu; DeLisa, Matthew P; Ke, Ailong
2012-10-19
The CRISPR (clustered regularly interspaced short palindromic repeats) system is a prokaryotic RNA-based adaptive immune system against extrachromosomal genetic elements. Cas2 is a universally conserved core CRISPR-associated protein required for the acquisition of new spacers for CRISPR adaptation. It was previously characterized as an endoribonuclease with preference for single-stranded (ss)RNA. Here, we show using crystallography, mutagenesis, and isothermal titration calorimetry that the Bacillus halodurans Cas2 (Bha_Cas2) from the subtype I-C/Dvulg CRISPR instead possesses metal-dependent endonuclease activity against double-stranded (ds)DNA. This activity is consistent with its putative function in producing new spacers for insertion into the 5'-end of the CRISPR locus. Mutagenesis and isothermal titration calorimetry studies revealed that a single divalent metal ion (Mg(2+) or Mn(2+)), coordinated by a symmetric Asp pair in the Bha_Cas2 dimer, is involved in the catalysis. We envision that a pH-dependent conformational change switches Cas2 into a metal-binding competent conformation for catalysis. We further propose that the distinct substrate preferences among Cas2 proteins may be determined by the sequence and structure in the β1-α1 loop.
Wehnes, C A; Rehberger, T G; Barrangou, R; Smith, A H
2014-10-01
Salmonella enterica ssp. enterica is a foodborne pathogen able to cause disease in both humans and animals. Diverse serovars of this pathogen exist, some of which are host specific, causing a range of clinical symptoms from asymptomatic infection through morbidity and mortality. According to a 2007 survey by the USDA National Animal Health Monitoring System, fecal shedding of Salmonella from healthy cows occurs on 39.7% of dairy farms in the United States. Certain serovars are frequently isolated from dairy farms and the majority of isolates from the National Animal Health Monitoring System study were represented by 5 serovars; however, genotypic diversity was not examined. The objective of this study was to determine the diversity of clustered regularly interspaced short palindromic repeats (CRISPR) loci in Salmonella collected from 8 dairy farms with a previous history of salmonellosis. None of the cows or calves sampled on 2 of the 8 dairy farms were shedding Salmonella, although Salmonella was detected in a cow bedding sample on 1 of these farms. Salmonella populations were discrete on each farm, according to CRISPR typing, with the exception of an Anatum var. 15+ type on farms 5 and 6 and the Montevideo type on farms 1 and 2. One to 4 distinct CRISPR genotypes were identified per farm. The CRISPR typing differed within serovars, as Montevideo, Anatum var. 15+, and Muenster serovars had no overlap of spacer content, even on the same farm, reflecting between- and within-serovar genetic diversity. The dynamic nature of Salmonella populations was shown in a farm that was sampled longitudinally over 13.5 mo. Changes in serovar from 3,19:-:z27 to Montevideo was observed between the first sampling time and 8 mo later, with concomitant change in CRISPR alleles. The results indicate that Salmonella strains present in smaller dairy herds (<500 head) are specific to that farm and new Salmonella strains may emerge over time. Copyright © 2014 American Dairy Science
Chen, Jing; Li, Tiancheng; Zhou, Xuedong; Cheng, Lei; Huo, Yuanyuan; Zou, Jing; Li, Yuqing
2017-11-01
The aim of this study was to analyze the characteristics of the clustered regularly interspaced short palindromic repeats (CRISPR) sites in 45 clinical Streptococcus mutans strains and their relationship to the clinical manifestations of early childhood caries (ECC). Forty-five S. mutans strains were isolated from the plaque samples taken from sixty-three children. CRISPR sites were sequenced and BLAST was used to compare these sites to those in the CRISPRTarget database. The association between the distribution of CRISPR sites and the manifestation of caries was analyzed by Chi-Square test. Further, biofilm formation (by crystal violet staining) and the synthesis of polysaccharide (by anthrone-sulfuric method) of all clinical isolated S. mutans strains with both CRISPR sites and no CRISPR site were comapared. Finally, acidogenicity and acidurity of two typical strains were determined using pH drop and acid tolerance assays. Biofilm formation and EPS synthesis by two typical strains were compared by 3D CLSM (Confocal Laser Scanning Microscope) assays and the expression of gtf genes were evaluated using qPCR. We found that most of the spacers in the clinical S. mutans strains were derived from Streptococcus phages APCM01 and M102. The number of CRISPR sites in these strains was associated with the clinical manifestations of ECC. Moreover, we found that the biofilm formation and EPS synthesis ability of the S. mutans strains with both CRISPR sites was significant improved. An association was found between the distribution of CRISPR sites and the clinical manifestations of caries. The CRISPR sites might contribute to the cariogenic potential of S. mutans. Copyright © 2017 Elsevier Ltd. All rights reserved.
DEFF Research Database (Denmark)
Lintner, Nathanael G; Kerou, Melina; Brumfield, Susan K
2011-01-01
In response to viral infection, many prokaryotes incorporate fragments of virus-derived DNA into loci called clustered regularly interspaced short palindromic repeats (CRISPRs). The loci are then transcribed, and the processed CRISPR transcripts are used to target invading viral DNA and RNA....... The Escherichia coli "CRISPR-associated complex for antiviral defense" (CASCADE) is central in targeting invading DNA. Here we report the structural and functional characterization of an archaeal CASCADE (aCASCADE) from Sulfolobus solfataricus. Tagged Csa2 (Cas7) expressed in S. solfataricus co-purifies with Cas5......a-, Cas6-, Csa5-, and Cas6-processed CRISPR-RNA (crRNA). Csa2, the dominant protein in aCASCADE, forms a stable complex with Cas5a. Transmission electron microscopy reveals a helical complex of variable length, perhaps due to substoichiometric amounts of other CASCADE components. A recombinant Csa2...
Canver, Matthew C.; Bauer, Daniel E.; Dass, Abhishek; Yien, Yvette Y.; Chung, Jacky; Masuda, Takeshi; Maeda, Takahiro; Paw, Barry H.; Orkin, Stuart H.
2014-01-01
The clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 nuclease system has provided a powerful tool for genome engineering. Double strand breaks may trigger nonhomologous end joining repair, leading to frameshift mutations, or homology-directed repair using an extrachromosomal template. Alternatively, genomic deletions may be produced by a pair of double strand breaks. The efficiency of CRISPR/Cas9-mediated genomic deletions has not been systematically explored. Here, we present a methodology for the production of deletions in mammalian cells, ranging from 1.3 kb to greater than 1 Mb. We observed a high frequency of intended genomic deletions. Nondeleted alleles are nonetheless often edited with inversions or small insertion/deletions produced at CRISPR recognition sites. Deleted alleles also typically include small insertion/deletions at predicted deletion junctions. We retrieved cells with biallelic deletion at a frequency exceeding that of probabilistic expectation. We demonstrate an inverse relationship between deletion frequency and deletion size. This work suggests that CRISPR/Cas9 is a robust system to produce a spectrum of genomic deletions to allow investigation of genes and genetic elements. PMID:24907273
Hatoum-Aslan, Asma; Maniv, Inbal; Marraffini, Luciano A
2011-12-27
Precise RNA processing is fundamental to all small RNA-mediated interference pathways. In prokaryotes, clustered, regularly interspaced, short palindromic repeats (CRISPR) loci encode small CRISPR RNAs (crRNAs) that protect against invasive genetic elements by antisense targeting. CRISPR loci are transcribed as a long precursor that is cleaved within repeat sequences by CRISPR-associated (Cas) proteins. In many organisms, this primary processing generates crRNA intermediates that are subject to additional nucleolytic trimming to render mature crRNAs of specific lengths. The molecular mechanisms underlying this maturation event remain poorly understood. Here, we defined the genetic requirements for crRNA primary processing and maturation in Staphylococcus epidermidis. We show that changes in the position of the primary processing site result in extended or diminished maturation to generate mature crRNAs of constant length. These results indicate that crRNA maturation occurs by a ruler mechanism anchored at the primary processing site. We also show that maturation is mediated by specific cas genes distinct from those genes involved in primary processing, showing that this event is directed by CRISPR/Cas loci.
Tasaki, E; Hirayama, J; Tazumi, A; Hayashi, K; Hara, Y; Ueno, H; Moore, J E; Millar, B C; Matsuda, M
2012-02-01
Novel clustered regularly-interspaced short palindromic repeats (CRISPRs) locus [7,500 base pairs (bp) in length] occurred in the urease-positive thermophilic Campylobacter (UPTC) Japanese isolate, CF89-12. The 7,500 bp gene loci consisted of the 5'-methylaminomethyl-2-thiouridylate methyltransferase gene, putative (P) CRISPR associated (p-Cas), putative open reading frames, Cas1 and Cas2, leader sequence region (146 bp), 12 CRISPRs consensus sequence repeats (each 36 bp) separated by a non-repetitive unique spacer region of similar length (26-31 bp) and the phosphatidyl glycerophosphatase A gene. When the CRISPRs loci in the UPTC CF89-12 and five C. jejuni isolates were compared with one another, these six isolates contained p-Cas, Cas1 and Cas2 within the loci. Four to 12 CRISPRs consensus sequence repeats separated by a non-repetitive unique spacer region occurred in six isolates and the nucleotide sequences of those repeats gave approximately 92-100% similarity with each other. However, no sequence similarity occurred in the unique spacer regions among these isolates. The putative σ(70) transcriptional promoter and the hypothetical ρ-independent terminator structures for the CRISPRs and Cas were detected. No in vivo transcription of p-Cas, Cas1 and Cas2 was confirmed in the UPTC cells.
Nam, Ki Hyun; Kurinov, Igor; Ke, Ailong
2011-09-02
Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated protein genes (cas genes) are widespread in bacteria and archaea. They form a line of RNA-based immunity to eradicate invading bacteriophages and malicious plasmids. A key molecular event during this process is the acquisition of new spacers into the CRISPR loci to guide the selective degradation of the matching foreign genetic elements. Csn2 is a Nmeni subtype-specific cas gene required for new spacer acquisition. Here we characterize the Enterococcus faecalis Csn2 protein as a double-stranded (ds-) DNA-binding protein and report its 2.7 Å tetrameric ring structure. The inner circle of the Csn2 tetrameric ring is ∼26 Å wide and populated with conserved lysine residues poised for nonspecific interactions with ds-DNA. Each Csn2 protomer contains an α/β domain and an α-helical domain; significant hinge motion was observed between these two domains. Ca(2+) was located at strategic positions in the oligomerization interface. We further showed that removal of Ca(2+) ions altered the oligomerization state of Csn2, which in turn severely decreased its affinity for ds-DNA. In summary, our results provided the first insight into the function of the Csn2 protein in CRISPR adaptation by revealing that it is a ds-DNA-binding protein functioning at the quaternary structure level and regulated by Ca(2+) ions.
Canver, Matthew C; Bauer, Daniel E; Dass, Abhishek; Yien, Yvette Y; Chung, Jacky; Masuda, Takeshi; Maeda, Takahiro; Paw, Barry H; Orkin, Stuart H
2014-08-01
The clustered regularly interspaced short [corrected] palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 nuclease system has provided a powerful tool for genome engineering. Double strand breaks may trigger nonhomologous end joining repair, leading to frameshift mutations, or homology-directed repair using an extrachromosomal template. Alternatively, genomic deletions may be produced by a pair of double strand breaks. The efficiency of CRISPR/Cas9-mediated genomic deletions has not been systematically explored. Here, we present a methodology for the production of deletions in mammalian cells, ranging from 1.3 kb to greater than 1 Mb. We observed a high frequency of intended genomic deletions. Nondeleted alleles are nonetheless often edited with inversions or small insertion/deletions produced at CRISPR recognition sites. Deleted alleles also typically include small insertion/deletions at predicted deletion junctions. We retrieved cells with biallelic deletion at a frequency exceeding that of probabilistic expectation. We demonstrate an inverse relationship between deletion frequency and deletion size. This work suggests that CRISPR/Cas9 is a robust system to produce a spectrum of genomic deletions to allow investigation of genes and genetic elements. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Toro, Magaly; Cao, Guojie; Ju, Wenting; Allard, Marc; Barrangou, Rodolphe; Zhao, Shaohua; Brown, Eric; Meng, Jianghong
2014-02-01
Shiga toxin-producing Escherichia coli (STEC) strains (n = 194) representing 43 serotypes and E. coli K-12 were examined for clustered regularly interspaced short palindromic repeat (CRISPR) arrays to study genetic relatedness among STEC serotypes. A subset of the strains (n = 81) was further analyzed for subtype I-E cas and virulence genes to determine a possible association of CRISPR elements with potential virulence. Four types of CRISPR arrays were identified. CRISPR1 and CRISPR2 were present in all strains tested; 1 strain also had both CRISPR3 and CRISPR4, whereas 193 strains displayed a short, combined array, CRISPR3-4. A total of 3,353 spacers were identified, representing 528 distinct spacers. The average length of a spacer was 32 bp. Approximately one-half of the spacers (54%) were unique and found mostly in strains of less common serotypes. Overall, CRISPR spacer contents correlated well with STEC serotypes, and identical arrays were shared between strains with the same H type (O26:H11, O103:H11, and O111:H11). There was no association identified between the presence of subtype I-E cas and virulence genes, but the total number of spacers had a negative correlation with potential pathogenicity (P CRISPR-cas system and potential virulence needs to be determined on a broader scale, and the biological link will need to be established.
Yang, Yue; Wang, Haicheng; Xu, Shuyu; Peng, Jing; Jiang, Jiuhui; Li, Cuiying
2015-08-01
To investigate the effect of the fibronectin extra domain A on the aggressiveness of salivary adenoid cystic carcinoma (SACC) cells, via the clustered regularly interspaced short palindromic repeats (CRISPR)/ associated proteins (Cas) system. One sgRNA was designed to target the upstream of the genome sequences of extra domain A(EDA) exon and the downstream. Then the sgRNA was linked into plasmid PX-330 and transfected into SACC-83 cells. PCR and DNA sequence were used to testify the knockout cells, and the monoclones of EDA absent SACC cells were selected (A+C-2, A+C-6, B+C-10). CCK-8 cell proliferation and invasion was then tested in control group and the experimental group. The sgRNA was successfully linked into PX-330 plasmid. Part of adenoid cystic carcinoma cells' SACC-83 genomic EDA exon was knocked out, and the knockdown efficiency was above 70%, but the total amount of fibronectin did not change significantly. Three monoclones of EDA absent SACC- 83 cells were successfully selected with diminished migration and proliferation. The CRISPR/Cas9 system was a simplified system with relatively high knockout efficiency and EDA knockout could inhibiting SACC cell's mobility and invasiveness.
Liu, Fenyun; Kariyawasam, Subhashinie; Jayarao, Bhushan M; Barrangou, Rodolphe; Gerner-Smidt, Peter; Ribot, Efrain M; Knabel, Stephen J; Dudley, Edward G
2011-07-01
Salmonella enterica subsp. enterica serovar Enteritidis is a major cause of food-borne salmonellosis in the United States. Two major food vehicles for S. Enteritidis are contaminated eggs and chicken meat. Improved subtyping methods are needed to accurately track specific strains of S. Enteritidis related to human salmonellosis throughout the chicken and egg food system. A sequence typing scheme based on virulence genes (fimH and sseL) and clustered regularly interspaced short palindromic repeats (CRISPRs)-CRISPR-including multi-virulence-locus sequence typing (designated CRISPR-MVLST)-was used to characterize 35 human clinical isolates, 46 chicken isolates, 24 egg isolates, and 63 hen house environment isolates of S. Enteritidis. A total of 27 sequence types (STs) were identified among the 167 isolates. CRISPR-MVLST identified three persistent and predominate STs circulating among U.S. human clinical isolates and chicken, egg, and hen house environmental isolates in Pennsylvania, and an ST that was found only in eggs and humans. It also identified a potential environment-specific sequence type. Moreover, cluster analysis based on fimH and sseL identified a number of clusters, of which several were found in more than one outbreak, as well as 11 singletons. Further research is needed to determine if CRISPR-MVLST might help identify the ecological origins of S. Enteritidis strains that contaminate chickens and eggs.
Lintner, Nathanael G; Kerou, Melina; Brumfield, Susan K; Graham, Shirley; Liu, Huanting; Naismith, James H; Sdano, Matthew; Peng, Nan; She, Qunxin; Copié, Valérie; Young, Mark J; White, Malcolm F; Lawrence, C Martin
2011-06-17
In response to viral infection, many prokaryotes incorporate fragments of virus-derived DNA into loci called clustered regularly interspaced short palindromic repeats (CRISPRs). The loci are then transcribed, and the processed CRISPR transcripts are used to target invading viral DNA and RNA. The Escherichia coli "CRISPR-associated complex for antiviral defense" (CASCADE) is central in targeting invading DNA. Here we report the structural and functional characterization of an archaeal CASCADE (aCASCADE) from Sulfolobus solfataricus. Tagged Csa2 (Cas7) expressed in S. solfataricus co-purifies with Cas5a-, Cas6-, Csa5-, and Cas6-processed CRISPR-RNA (crRNA). Csa2, the dominant protein in aCASCADE, forms a stable complex with Cas5a. Transmission electron microscopy reveals a helical complex of variable length, perhaps due to substoichiometric amounts of other CASCADE components. A recombinant Csa2-Cas5a complex is sufficient to bind crRNA and complementary ssDNA. The structure of Csa2 reveals a crescent-shaped structure unexpectedly composed of a modified RNA-recognition motif and two additional domains present as insertions in the RNA-recognition motif. Conserved residues indicate potential crRNA- and target DNA-binding sites, and the H160A variant shows significantly reduced affinity for crRNA. We propose a general subunit architecture for CASCADE in other bacteria and Archaea.
Cheng, Man; Jin, Xubin; Mu, Lili; Wang, Fangyu; Li, Wei; Zhong, Xiaoling; Liu, Xuan; Shen, Wenchen; Liu, Ying; Zhou, Yan
2016-09-01
In utero electroporation (IUE) is commonly used to study cortical development of cerebrum by downregulating or overexpressing genes of interest in neural progenitor cells (NPCs) of small mammals. However, exogenous plasmids are lost or diluted over time. Furthermore, gene knockdown based on short-hairpin RNAs may exert nonspecific effects that lead to aberrant neuronal migration. Genomic engineering by the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system has great research and therapeutic potentials. Here we integrate the CRISPR/Cas9 components into the piggyBac (PB) transposon system (the CRISPR/Cas9-PB toolkit) for cortical IUEs. The mouse Sry-related HMG box-2 (Sox2) gene was selected as the target for its application. Most transduced cortical NPCs were depleted of SOX2 protein as early as 3 days post-IUE, whereas expressions of SOX1 and PAX6 remained intact. Furthermore, both the WT Cas9 and the D10A nickase mutant Cas9n showed comparable knockout efficiency. Transduced cortical cells were purified with fluorescence-activated cell sorting, and effective gene editing at the Sox2 loci was confirmed. Thus, application of the CRISPR/Cas9-PB toolkit in IUE is a promising strategy to study gene functions in cortical NPCs and their progeny. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Chen, Shuqing; Hou, Chengxiang; Bi, Honglun; Wang, Yueqiang; Xu, Jun; Li, Muwang; James, Anthony A; Huang, Yongping; Tan, Anjiang
2017-04-15
We developed a novel antiviral strategy by combining transposon-based transgenesis and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system for the direct cleavage of Bombyx mori nucleopolyhedrovirus (BmNPV) genome DNA to promote virus clearance in silkworms. We demonstrate that transgenic silkworms constitutively expressing Cas9 and guide RNAs targeting the BmNPV immediate early-1 ( ie-1 ) and me53 genes effectively induce target-specific cleavage and subsequent mutagenesis, especially large (∼7-kbp) segment deletions in BmNPV genomes, and thus exhibit robust suppression of BmNPV proliferation. Transgenic animals exhibited higher and inheritable resistance to BmNPV infection than wild-type animals. Our approach will not only contribute to modern sericulture but also shed light on future antiviral therapy. IMPORTANCE Pathogen genome targeting has shown its potential in antiviral research. However, transgenic CRISPR/Cas9 system-mediated viral genome targeting has not been reported as an antiviral strategy in a natural animal host of a virus. Our data provide an effective approach against BmNPV infection in a real-world biological system and demonstrate the potential of transgenic CRISPR/Cas9 systems in antiviral research in other species. Copyright © 2017 Chen et al.
Energy Technology Data Exchange (ETDEWEB)
Nam, Ki Hyun; Kurinov, Igor; Ke, Ailong (Cornell); (NWU)
2012-05-22
Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated protein genes (cas genes) are widespread in bacteria and archaea. They form a line of RNA-based immunity to eradicate invading bacteriophages and malicious plasmids. A key molecular event during this process is the acquisition of new spacers into the CRISPR loci to guide the selective degradation of the matching foreign genetic elements. Csn2 is a Nmeni subtype-specific cas gene required for new spacer acquisition. Here we characterize the Enterococcus faecalis Csn2 protein as a double-stranded (ds-) DNA-binding protein and report its 2.7 {angstrom} tetrameric ring structure. The inner circle of the Csn2 tetrameric ring is {approx}26 {angstrom} wide and populated with conserved lysine residues poised for nonspecific interactions with ds-DNA. Each Csn2 protomer contains an {alpha}/{beta} domain and an {alpha}-helical domain; significant hinge motion was observed between these two domains. Ca{sup 2+} was located at strategic positions in the oligomerization interface. We further showed that removal of Ca{sup 2+} ions altered the oligomerization state of Csn2, which in turn severely decreased its affinity for ds-DNA. In summary, our results provided the first insight into the function of the Csn2 protein in CRISPR adaptation by revealing that it is a ds-DNA-binding protein functioning at the quaternary structure level and regulated by Ca{sup 2+} ions.
Kato-Inui, Tomoko; Takahashi, Gou; Hsu, Szuyin; Miyaoka, Yuichiro
2018-05-18
Genome editing using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) predominantly induces non-homologous end joining (NHEJ), which generates random insertions or deletions, whereas homology-directed repair (HDR), which generates precise recombination products, is useful for wider applications. However, the factors that determine the ratio of HDR to NHEJ products after CRISPR/Cas9 editing remain unclear, and methods by which the proportion of HDR products can be increased have not yet been fully established. We systematically analyzed the HDR and NHEJ products after genome editing using various modified guide RNAs (gRNAs) and Cas9 variants with an enhanced conformational checkpoint to improve the fidelity at endogenous gene loci in HEK293T cells and HeLa cells. We found that these modified gRNAs and Cas9 variants were able to enhance HDR in both single-nucleotide substitutions and a multi-kb DNA fragment insertion. Our results suggest that the original CRISPR/Cas9 system from the bacterial immune system is not necessarily the best option for the induction of HDR in genome editing and indicate that the modulation of the kinetics of conformational checkpoints of Cas9 can optimize the HDR/NHEJ ratio.
Mulepati, Sabin; Bailey, Scott
2011-09-09
RNA transcribed from clustered regularly interspaced short palindromic repeats (CRISPRs) protects many prokaryotes from invasion by foreign DNA such as viruses, conjugative plasmids, and transposable elements. Cas3 (CRISPR-associated protein 3) is essential for this CRISPR protection and is thought to mediate cleavage of the foreign DNA through its N-terminal histidine-aspartate (HD) domain. We report here the 1.8 Å crystal structure of the HD domain of Cas3 from Thermus thermophilus HB8. Structural and biochemical studies predict that this enzyme binds two metal ions at its active site. We also demonstrate that the single-stranded DNA endonuclease activity of this T. thermophilus domain is activated not by magnesium but by transition metal ions such as manganese and nickel. Structure-guided mutagenesis confirms the importance of the metal-binding residues for the nuclease activity and identifies other active site residues. Overall, these results provide a framework for understanding the role of Cas3 in the CRISPR system.
Yosef, Ido; Goren, Moran G; Kiro, Ruth; Edgar, Rotem; Qimron, Udi
2011-12-13
Prokaryotic DNA arrays arranged as clustered regularly interspaced short palindromic repeats (CRISPR), along with their associated proteins, provide prokaryotes with adaptive immunity by RNA-mediated targeting of alien DNA or RNA matching the sequences between the repeats. Here, we present a thorough screening system for the identification of bacterial proteins participating in immunity conferred by the Escherichia coli CRISPR system. We describe the identification of one such protein, high-temperature protein G (HtpG), a homolog of the eukaryotic chaperone heat-shock protein 90. We demonstrate that in the absence of htpG, the E. coli CRISPR system loses its suicidal activity against λ prophage and its ability to provide immunity from lysogenization. Transcomplementation of htpG restores CRISPR activity. We further show that inactivity of the CRISPR system attributable to htpG deficiency can be suppressed by expression of Cas3, a protein that is essential for its activity. Accordingly, we also find that the steady-state level of overexpressed Cas3 is significantly enhanced following HtpG expression. We conclude that HtpG is a newly identified positive modulator of the CRISPR system that is essential for maintaining functional levels of Cas3.
Kuno, Sotaro; Yoshida, Takashi; Kaneko, Takakazu; Sako, Yoshihiko
2012-08-01
Clustered regularly interspaced short palindromic repeats (CRISPR) confer sequence-dependent, adaptive resistance in prokaryotes against viruses and plasmids via incorporation of short sequences, called spacers, derived from foreign genetic elements. CRISPR loci are thus considered to provide records of past infections. To describe the host-parasite (i.e., cyanophages and plasmids) interactions involving the bloom-forming freshwater cyanobacterium Microcystis aeruginosa, we investigated CRISPR in four M. aeruginosa strains and in two previously sequenced genomes. The number of spacers in each locus was larger than the average among prokaryotes. All spacers were strain specific, except for a string of 11 spacers shared in two closely related strains, suggesting diversification of the loci. Using CRISPR repeat-based PCR, 24 CRISPR genotypes were identified in a natural cyanobacterial community. Among 995 unique spacers obtained, only 10 sequences showed similarity to M. aeruginosa phage Ma-LMM01. Of these, six spacers showed only silent or conservative nucleotide mutations compared to Ma-LMM01 sequences, suggesting a strategy by the cyanophage to avert CRISPR immunity dependent on nucleotide identity. These results imply that host-phage interactions can be divided into M. aeruginosa-cyanophage combinations rather than pandemics of population-wide infectious cyanophages. Spacer similarity also showed frequent exposure of M. aeruginosa to small cryptic plasmids that were observed only in a few strains. Thus, the diversification of CRISPR implies that M. aeruginosa has been challenged by diverse communities (almost entirely uncharacterized) of cyanophages and plasmids.
Maier, Lisa-Katharina; Stachler, Aris-Edda; Saunders, Sita J.; Backofen, Rolf; Marchfelder, Anita
2015-01-01
The prokaryotic immune system CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated) is a defense system that protects prokaryotes against foreign DNA. The short CRISPR RNAs (crRNAs) are central components of this immune system. In CRISPR-Cas systems type I and III, crRNAs are generated by the endonuclease Cas6. We developed a Cas6b-independent crRNA maturation pathway for the Haloferax type I-B system in vivo that expresses a functional crRNA, which we termed independently generated crRNA (icrRNA). The icrRNA is effective in triggering degradation of an invader plasmid carrying the matching protospacer sequence. The Cas6b-independent maturation of the icrRNA allowed mutation of the repeat sequence without interfering with signals important for Cas6b processing. We generated 23 variants of the icrRNA and analyzed them for activity in the interference reaction. icrRNAs with deletions or mutations of the 3′ handle are still active in triggering an interference reaction. The complete 3′ handle could be removed without loss of activity. However, manipulations of the 5′ handle mostly led to loss of interference activity. Furthermore, we could show that in the presence of an icrRNA a strain without Cas6b (Δcas6b) is still active in interference. PMID:25512373
Maier, Lisa-Katharina; Stachler, Aris-Edda; Saunders, Sita J; Backofen, Rolf; Marchfelder, Anita
2015-02-13
The prokaryotic immune system CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated) is a defense system that protects prokaryotes against foreign DNA. The short CRISPR RNAs (crRNAs) are central components of this immune system. In CRISPR-Cas systems type I and III, crRNAs are generated by the endonuclease Cas6. We developed a Cas6b-independent crRNA maturation pathway for the Haloferax type I-B system in vivo that expresses a functional crRNA, which we termed independently generated crRNA (icrRNA). The icrRNA is effective in triggering degradation of an invader plasmid carrying the matching protospacer sequence. The Cas6b-independent maturation of the icrRNA allowed mutation of the repeat sequence without interfering with signals important for Cas6b processing. We generated 23 variants of the icrRNA and analyzed them for activity in the interference reaction. icrRNAs with deletions or mutations of the 3' handle are still active in triggering an interference reaction. The complete 3' handle could be removed without loss of activity. However, manipulations of the 5' handle mostly led to loss of interference activity. Furthermore, we could show that in the presence of an icrRNA a strain without Cas6b (Δcas6b) is still active in interference. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
Tong, Zhongchun; Du, Yu; Ling, Junqi; Huang, Lijia; Ma, Jinglei
2017-12-01
A high prevalence of Enterococcus faecalis ( E. faecalis ) is observed in teeth with root canal treatment failures. Clustered regularly interspaced short palindromic repeats (CRISPR) are widely distributed in prokaryotes that have adaptive immune systems against mobile elements, including pathogenic genes. The present study investigated the relevance of the CRISPR in E. faecalis strains isolated from retreated root canals on biofilms, periapical lesions and drug resistance. A total of 20 E. faecalis strains were extracted from the root canals of teeth referred for root canal retreatment. CRISPR-Cas loci were identified by two pairs of relevant primers and polymerase chain reaction. The susceptibility of the 20 isolated strains to intracanal irrigants was evaluated by 1- and 5-minute challenges with a mixture of a tetracycline isomer, an acid and a detergent (MTAD), 2% chlorhexidine (CHX) and 5.25% sodium hypochlorite (NaOCl). The microtiter plate assay and crystal violet staining were used to compare the biofilm formation of the E. faecalis isolate strains. Out of the 20 E. faecalis isolate strains, 5 strains that lacked CRISPR-cas determinants exhibited significant periapical lesions. Among the 15 strains containing CRISPR-cas determinants, 8 were isolated from root canals with inadequate fillings and 7 were isolated from root canals without any fillings. The five strains lacking CRISPR-cas loci were observed to be more resistant to MTAD and 2% CHX than the 15 strains that had CRISPR-cas loci. All of the strains exhibited the same susceptibility to 5.25% NaOCl. Furthermore, the 5 strains lacking CRISPR-cas determinants generated more biofilm than the other 15 strains. Thus, the results of the present study suggested that E. faecalis root canal isolates lacking CRISPR-cas exhibit higher resistance to intracanal irrigants, stronger biofilm formation and generate significant periapical lesions.
Yin, Shuang; Jensen, Mark A; Bai, Jiawei; Debroy, Chitrita; Barrangou, Rodolphe; Dudley, Edward G
2013-09-01
The Shiga toxin-producing Escherichia coli (STEC) strains, including those of O157:H7 and the "big six" serogroups (i.e., serogroups O26, O45, O103, O111, O121, and O145), are a group of pathogens designated food adulterants in the United States. The relatively conserved nature of clustered regularly interspaced short palindromic repeats (CRISPRs) in phylogenetically related E. coli strains makes them potential subtyping markers for STEC detection, and a quantitative PCR (qPCR)-based assay was previously developed for O26:H11, O45:H2, O103:H2, O111:H8, O121:H19, O145:H28, and O157:H7 isolates. To better evaluate the sensitivity and specificity of this qPCR method, the CRISPR loci of 252 O157 and big-six STEC isolates were sequenced and analyzed along with 563 CRISPR1 and 624 CRISPR2 sequences available in GenBank. General conservation of spacer content and order was observed within each O157 and big-six serogroup, validating the qPCR method. Meanwhile, it was found that spacer deletion, the presence of an insertion sequence, and distinct alleles within a serogroup are sources of false-negative reactions. Conservation of CRISPR arrays among isolates expressing the same flagellar antigen, specifically, H7, H2, and H11, suggested that these isolates share an ancestor and provided an explanation for the false positives previously observed in the qPCR results. An analysis of spacer distribution across E. coli strains provided limited evidence for temporal spacer acquisition. Conversely, comparison of CRISPR sequences between strains along the stepwise evolution of O157:H7 from its O55:H7 ancestor revealed that, over this ∼7,000-year span, spacer deletion was the primary force generating CRISPR diversity.
Ren, Lu; Deng, Lin-Hua; Zhang, Ri-Peng; Wang, Cheng-Dong; Li, De-Sheng; Xi, Li-Xin; Chen, Zhen-Rong; Yang, Rui; Huang, Jie; Zeng, Yang-Ru; Wu, Hong-Lin; Cao, San-Jie; Wu, Rui; Huang, Yong; Yan, Qi-Gui
2017-02-01
To detect drug resistance in Shigella obtained from the dung of the giant panda, explore the factors leading to drug resistance in Shigella, understand the characteristics of clustered, regularly interspaced, short, palindromic repeats (CRISPR), and assess the relationship between CRISPR and drug resistance. We collected fresh feces from 27 healthy giant pandas in the Giant Panda Conservation base (Wolong, China). We identified the strains of Shigella in the samples by using nucleotide sequence analysis. Further, the Kirby-Bauer paper method was used to determine drug sensitivity of the Shigella strains. CRISPR-associated protein genes cas1 and cas2 in Shigella were detected by polymerase chain reaction (PCR), and the PCR products were sequenced and compared. We isolated and identified 17 strains of Shigella from 27 samples, including 14 strains of Shigella flexneri, 2 strains of Shigella sonnei, and 1 strain of Shigella dysenteriae. Further, drug resistance to cefazolin, imipenem, and amoxicillin-clavulanic acid was identified as a serious problem, as multidrug-resistant strains were detected. Further, cas1 and cas2 showed different degrees of point mutations. The CRISPR system widely exists in Shigella and shares homology with that in Escherichia coli. The cas1 and cas 2 mutations contribute to the different levels of resistance. Point mutations at sites 3176455, 3176590, and 3176465 in cas1 (a); sites 3176989, 3176992, and 3176995 in cas1 (b); sites 3176156 and 3176236 in cas2 may affect the resistance of bacteria, cause emergence of multidrug resistance, and increase the types of drug resistance.
Mandai, Shintaro; Mori, Takayasu; Sohara, Eisei; Rai, Tatemitsu; Uchida, Shinichi
2015-12-01
Previous genome-wide association studies identified serine threonine kinase 39 (STK39), encoding STE20/SPS1-related proline/alanine-rich kinase, as one of a limited number of hypertension susceptibility genes. A recent meta-analysis confirmed the association of STK39 intronic polymorphism rs3754777 with essential hypertension, among previously reported hypertension-associated STK39 polymorphisms. However, the biochemical function of this polymorphism in the mechanism responsible for hypertension is yet to be clarified. We generated rs3754777G>A knockin human cell lines with clustered regularly interspaced short palindromic repeats-mediated genome engineering. Homozygous (A/A) and heterozygous (G/A) knockin human embryonic kidney cell lines were generated using a double nickase, single-guide RNAs targeting STK39 intron 5 around single-nucleotide polymorphism, and a 100-bp donor single-stranded DNA oligonucleotide. Reverse transcription polymerase chain reaction with sequencing analyses revealed the identical STK39 transcripts among the wild-type and both knockin cell lines. Quantitative reverse transcription polymerase chain reaction showed increased STK39 mRNA expression, and immunoblot analysis revealed increases in total and phosphorylated STE20/SPS1-related proline/alanine-rich kinase with increased phosphorylated Na-K-Cl cotransporter isoform 1 in both knockin cell lines. The largest increases in these molecules were observed in the homozygous cell line. These findings indicated that this intronic polymorphism increases STK39 transcription, leading to activation of the STE20/SPS1-related proline/alanine-rich kinase-solute carrier family 12A signaling cascade. Increased interactions between STE20/SPS1-related proline/alanine-rich kinase and the target cation-chloride cotransporters may be responsible for hypertension susceptibility in individuals with this polymorphism. © 2015 American Heart Association, Inc.
Ostria-Hernández, Martha Lorena; Sánchez-Vallejo, Carlos Javier; Ibarra, J Antonio; Castro-Escarpulli, Graciela
2015-08-04
In recent years the emergence of multidrug resistant Klebsiella pneumoniae strains has been an increasingly common event. This opportunistic species is one of the five main bacterial pathogens that cause hospital infections worldwide and multidrug resistance has been associated with the presence of high molecular weight plasmids. Plasmids are generally acquired through horizontal transfer and therefore is possible that systems that prevent the entry of foreign genetic material are inactive or absent. One of these systems is CRISPR/Cas. However, little is known regarding the clustered regularly interspaced short palindromic repeats and their associated Cas proteins (CRISPR/Cas) system in K. pneumoniae. The adaptive immune system CRISPR/Cas has been shown to limit the entry of foreign genetic elements into bacterial organisms and in some bacteria it has been shown to be involved in regulation of virulence genes. Thus in this work we used bioinformatics tools to determine the presence or absence of CRISPR/Cas systems in available K. pneumoniae genomes. The complete CRISPR/Cas system was identified in two out of the eight complete K. pneumoniae genomes sequences and in four out of the 44 available draft genomes sequences. The cas genes in these strains comprises eight cas genes similar to those found in Escherichia coli, suggesting they belong to the type I-E group, although their arrangement is slightly different. As for the CRISPR sequences, the average lengths of the direct repeats and spacers were 29 and 33 bp, respectively. BLAST searches demonstrated that 38 of the 116 spacer sequences (33%) are significantly similar to either plasmid, phage or genome sequences, while the remaining 78 sequences (67%) showed no significant similarity to other sequences. The region where the CRISPR/Cas systems were located is the same in all the Klebsiella genomes containing it, it has a syntenic architecture, and is located among genes encoding for proteins likely involved in
Hargreaves, Katherine R; Flores, Cesar O; Lawley, Trevor D; Clokie, Martha R J
2014-08-26
Clostridium difficile is an important human-pathogenic bacterium causing antibiotic-associated nosocomial infections worldwide. Mobile genetic elements and bacteriophages have helped shape C. difficile genome evolution. In many bacteria, phage infection may be controlled by a form of bacterial immunity called the clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR/Cas) system. This uses acquired short nucleotide sequences (spacers) to target homologous sequences (protospacers) in phage genomes. C. difficile carries multiple CRISPR arrays, and in this paper we examine the relationships between the host- and phage-carried elements of the system. We detected multiple matches between spacers and regions in 31 C. difficile phage and prophage genomes. A subset of the spacers was located in prophage-carried CRISPR arrays. The CRISPR spacer profiles generated suggest that related phages would have similar host ranges. Furthermore, we show that C. difficile strains of the same ribotype could either have similar or divergent CRISPR contents. Both synonymous and nonsynonymous mutations in the protospacer sequences were identified, as well as differences in the protospacer adjacent motif (PAM), which could explain how phages escape this system. This paper illustrates how the distribution and diversity of CRISPR spacers in C. difficile, and its prophages, could modulate phage predation for this pathogen and impact upon its evolution and pathogenicity. Clostridium difficile is a significant bacterial human pathogen which undergoes continual genome evolution, resulting in the emergence of new virulent strains. Phages are major facilitators of genome evolution in other bacterial species, and we use sequence analysis-based approaches in order to examine whether the CRISPR/Cas system could control these interactions across divergent C. difficile strains. The presence of spacer sequences in prophages that are homologous to phage genomes raises an
Heussler, Gary E; Cady, Kyle C; Koeppen, Katja; Bhuju, Sabin; Stanton, Bruce A; O'Toole, George A
2015-05-12
The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (CRISPR/Cas) system is an adaptive immune system present in many archaea and bacteria. CRISPR/Cas systems are incredibly diverse, and there is increasing evidence of CRISPR/Cas systems playing a role in cellular functions distinct from phage immunity. Previously, our laboratory reported one such alternate function in which the type 1-F CRISPR/Cas system of the opportunistic pathogen Pseudomonas aeruginosa strain UCBPP-PA14 (abbreviated as P. aeruginosa PA14) inhibits both biofilm formation and swarming motility when the bacterium is lysogenized by the bacteriophage DMS3. In this study, we demonstrated that the presence of just the DMS3 protospacer and the protospacer-adjacent motif (PAM) on the P. aeruginosa genome is necessary and sufficient for this CRISPR-dependent loss of these group behaviors, with no requirement of additional DMS3 sequences. We also demonstrated that the interaction of the CRISPR system with the DMS3 protospacer induces expression of SOS-regulated phage-related genes, including the well-characterized pyocin operon, through the activity of the nuclease Cas3 and subsequent RecA activation. Furthermore, our data suggest that expression of the phage-related genes results in bacterial cell death on a surface due to the inability of the CRISPR-engaged strain to downregulate phage-related gene expression, while these phage-related genes have minimal impact on growth and viability under planktonic conditions. Deletion of the phage-related genes restores biofilm formation and swarming motility while still maintaining a functional CRISPR/Cas system, demonstrating that the loss of these group behaviors is an indirect effect of CRISPR self-targeting. The various CRISPR/Cas systems found in both archaea and bacteria are incredibly diverse, and advances in understanding the complex mechanisms of these varied systems has not only increased our knowledge of host
van Duijn, Esther; Barbu, Ioana M; Barendregt, Arjan; Jore, Matthijs M; Wiedenheft, Blake; Lundgren, Magnus; Westra, Edze R; Brouns, Stan J J; Doudna, Jennifer A; van der Oost, John; Heck, Albert J R
2012-11-01
The CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated genes) immune system of bacteria and archaea provides acquired resistance against viruses and plasmids, by a strategy analogous to RNA-interference. Key components of the defense system are ribonucleoprotein complexes, the composition of which appears highly variable in different CRISPR/Cas subtypes. Previous studies combined mass spectrometry, electron microscopy, and small angle x-ray scattering to demonstrate that the E. coli Cascade complex (405 kDa) and the P. aeruginosa Csy-complex (350 kDa) are similar in that they share a central spiral-shaped hexameric structure, flanked by associating proteins and one CRISPR RNA. Recently, a cryo-electron microscopy structure of Cascade revealed that the CRISPR RNA molecule resides in a groove of the hexameric backbone. For both complexes we here describe the use of native mass spectrometry in combination with ion mobility mass spectrometry to assign a stable core surrounded by more loosely associated modules. Via computational modeling subcomplex structures were proposed that relate to the experimental IMMS data. Despite the absence of obvious sequence homology between several subunits, detailed analysis of sub-complexes strongly suggests analogy between subunits of the two complexes. Probing the specific association of E. coli Cascade/crRNA to its complementary DNA target reveals a conformational change. All together these findings provide relevant new information about the potential assembly process of the two CRISPR-associated complexes.
Duan, Yajian; Ma, Gaoen; Huang, Xionggao; D'Amore, Patricia A; Zhang, Feng; Lei, Hetian
2016-07-29
The G309 allele of SNPs in the mouse double minute (MDM2) promoter locus is associated with a higher risk of cancer and proliferative vitreoretinopathy (PVR), but whether SNP G309 contributes to the pathogenesis of PVR is to date unknown. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease (Cas) 9 from Streptococcus pyogenes (SpCas9) can be harnessed to manipulate a single or multiple nucleotides in mammalian cells. Here we delivered SpCas9 and guide RNAs using dual adeno-associated virus-derived vectors to target the MDM2 genomic locus together with a homologous repair template for creating the mutation of MDM2 T309G in human primary retinal pigment epithelial (hPRPE) cells whose genotype is MDM2 T309T. The next-generation sequencing results indicated that there was 42.51% MDM2 G309 in the edited hPRPE cells using adeno-associated viral CRISPR/Cas9. Our data showed that vitreous induced an increase in MDM2 and subsequent attenuation of p53 expression in MDM2 T309G hPRPE cells. Furthermore, our experimental results demonstrated that MDM2 T309G in hPRPE cells enhanced vitreous-induced cell proliferation and survival, suggesting that this SNP contributes to the pathogenesis of PVR. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Brendel, Jutta; Stoll, Britta; Lange, Sita J; Sharma, Kundan; Lenz, Christof; Stachler, Aris-Edda; Maier, Lisa-Katharina; Richter, Hagen; Nickel, Lisa; Schmitz, Ruth A; Randau, Lennart; Allers, Thorsten; Urlaub, Henning; Backofen, Rolf; Marchfelder, Anita
2014-03-07
The clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR-Cas) system is a prokaryotic defense mechanism against foreign genetic elements. A plethora of CRISPR-Cas versions exist, with more than 40 different Cas protein families and several different molecular approaches to fight the invading DNA. One of the key players in the system is the CRISPR-derived RNA (crRNA), which directs the invader-degrading Cas protein complex to the invader. The CRISPR-Cas types I and III use the Cas6 protein to generate mature crRNAs. Here, we show that the Cas6 protein is necessary for crRNA production but that additional Cas proteins that form a CRISPR-associated complex for antiviral defense (Cascade)-like complex are needed for crRNA stability in the CRISPR-Cas type I-B system in Haloferax volcanii in vivo. Deletion of the cas6 gene results in the loss of mature crRNAs and interference. However, cells that have the complete cas gene cluster (cas1-8b) removed and are transformed with the cas6 gene are not able to produce and stably maintain mature crRNAs. crRNA production and stability is rescued only if cas5, -6, and -7 are present. Mutational analysis of the cas6 gene reveals three amino acids (His-41, Gly-256, and Gly-258) that are essential for pre-crRNA cleavage, whereas the mutation of two amino acids (Ser-115 and Ser-224) leads to an increase of crRNA amounts. This is the first systematic in vivo analysis of Cas6 protein variants. In addition, we show that the H. volcanii I-B system contains a Cascade-like complex with a Cas7, Cas5, and Cas6 core that protects the crRNA.
Brendel, Jutta; Stoll, Britta; Lange, Sita J.; Sharma, Kundan; Lenz, Christof; Stachler, Aris-Edda; Maier, Lisa-Katharina; Richter, Hagen; Nickel, Lisa; Schmitz, Ruth A.; Randau, Lennart; Allers, Thorsten; Urlaub, Henning; Backofen, Rolf; Marchfelder, Anita
2014-01-01
The clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR-Cas) system is a prokaryotic defense mechanism against foreign genetic elements. A plethora of CRISPR-Cas versions exist, with more than 40 different Cas protein families and several different molecular approaches to fight the invading DNA. One of the key players in the system is the CRISPR-derived RNA (crRNA), which directs the invader-degrading Cas protein complex to the invader. The CRISPR-Cas types I and III use the Cas6 protein to generate mature crRNAs. Here, we show that the Cas6 protein is necessary for crRNA production but that additional Cas proteins that form a CRISPR-associated complex for antiviral defense (Cascade)-like complex are needed for crRNA stability in the CRISPR-Cas type I-B system in Haloferax volcanii in vivo. Deletion of the cas6 gene results in the loss of mature crRNAs and interference. However, cells that have the complete cas gene cluster (cas1–8b) removed and are transformed with the cas6 gene are not able to produce and stably maintain mature crRNAs. crRNA production and stability is rescued only if cas5, -6, and -7 are present. Mutational analysis of the cas6 gene reveals three amino acids (His-41, Gly-256, and Gly-258) that are essential for pre-crRNA cleavage, whereas the mutation of two amino acids (Ser-115 and Ser-224) leads to an increase of crRNA amounts. This is the first systematic in vivo analysis of Cas6 protein variants. In addition, we show that the H. volcanii I-B system contains a Cascade-like complex with a Cas7, Cas5, and Cas6 core that protects the crRNA. PMID:24459147
Lai, Frank Pui-Ling; Lau, Sin-Ting; Wong, John Kwong-Leong; Gui, Hongsheng; Wang, Reeson Xu; Zhou, Tingwen; Lai, Wing Hon; Tse, Hung-Fat; Tam, Paul Kwong-Hang; Garcia-Barcelo, Maria-Mercedes; Ngan, Elly Sau-Wai
2017-07-01
Hirschsprung disease is caused by failure of enteric neural crest cells (ENCCs) to fully colonize the bowel, leading to bowel obstruction and megacolon. Heterozygous mutations in the coding region of the RET gene cause a severe form of Hirschsprung disease (total colonic aganglionosis). However, 80% of HSCR patients have short-segment Hirschsprung disease (S-HSCR), which has not been associated with genetic factors. We sought to identify mutations associated with S-HSCR, and used the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system to determine how mutations affect ENCC function. We created induced pluripotent stem cell (iPSC) lines from 1 patient with total colonic aganglionosis (with the G731del mutation in RET) and from 2 patients with S-HSCR (without a RET mutation), as well as RET +/- and RET -/- iPSCs. IMR90-iPSC cells were used as the control cell line. Migration and differentiation capacities of iPSC-derived ENCCs were analyzed in differentiation and migration assays. We searched for mutation(s) associated with S-HSCR by combining genetic and transcriptome data from patient blood- and iPSC-derived ENCCs, respectively. Mutations in the iPSCs were corrected using the CRISPR/Cas9 system. ENCCs derived from all iPSC lines, but not control iPSCs, had defects in migration and neuronal lineage differentiation. RET mutations were associated with differentiation and migration defects of ENCCs in vitro. Genetic and transcriptome analyses associated a mutation in the vinculin gene (VCL M209L) with S-HSCR. CRISPR/Cas9 correction of the RET G731del and VCL M209L mutations in iPSCs restored the differentiation and migration capacities of ENCCs. We identified mutations in VCL associated with S-HSCR. Correction of this mutation in iPSC using CRISPR/Cas9 editing, as well as the RET G731del mutation that causes Hirschsprung disease with total colonic aganglionosis, restored ENCC function. Our study demonstrates how human iPSCs can
Tanaka, R; Murakami, H; Ote, M; Yamamoto, D
2016-08-01
How behavioural diversity emerged in evolution is an unexplored subject in biology. To tackle this problem, genes and circuits for a behaviour need to be determined in different species for phylogenetic comparisons. The recently developed clustered regulatory interspaced short palindromic repeats/CRISPR associated protein9 (CRISPR/Cas9) system made such a challenge possible by providing the means to induce mutations in a gene of interest in any organism. Aiming at elucidating diversification in genetic and neural networks for courtship behaviour, we attempted to generate a genetic tool kit in Drosophila subobscura, a nonmodel species distantly related to the genetic model Drosophila melanogaster. Here we report the generation of yellow (y) and white mutations with the aid of the CRISPR/Cas9 system, and the rescue of the y mutant phenotype by germline transformation of the newly established y mutant fly line with a y(+) -marked piggyBac vector. This successful mutagenesis and transformation in D. subobscura open up an avenue for comprehensive genetic analyses of higher functions in this and other nonmodel Drosophila species, representing a key step toward systematic comparisons of genes and circuitries underlying behaviour amongst species. © 2016 The Royal Entomological Society.
Huang, Mengqi; Zhou, Xiaoming; Wang, Huiying; Xing, Da
2018-02-06
A novel CRISPR/Cas9 triggered isothermal exponential amplification reaction (CAS-EXPAR) strategy based on CRISPR/Cas9 cleavage and nicking endonuclease (NEase) mediated nucleic acids amplification was developed for rapid and site-specific nucleic acid detection. CAS-EXPAR was primed by the target DNA fragment produced by cleavage of CRISPR/Cas9, and the amplification reaction performed cyclically to generate a large number of DNA replicates which were detected using a real-time fluorescence monitoring method. This strategy that combines the advantages of CRISPR/Cas9 and exponential amplification showed high specificity as well as rapid amplification kinetics. Unlike conventional nucleic acids amplification reactions, CAS-EXPAR does not require exogenous primers, which often cause target-independent amplification. Instead, primers are first generated by Cas9/sgRNA directed site-specific cleavage of target and accumulated during the reaction. It was demonstrated this strategy gave a detection limit of 0.82 amol and showed excellent specificity in discriminating single-base mismatch. Moreover, the applicability of this method to detect DNA methylation and L. monocytogenes total RNA was also verified. Therefore, CAS-EXPAR may provide a new paradigm for efficient nucleic acid amplification and hold the potential for molecular diagnostic applications.
Li, Wan; Bian, Xin; Evivie, Smith Etareri; Huo, Gui-Cheng
2016-09-01
The CRISPR-Cas (CRISPR together with CRISPR-associated proteins) modules are the adaptive immune system, acting as an adaptive and heritable immune system in bacteria and archaea. CRISPR-based immunity acts by integrating short virus sequences in the cell's CRISPR locus, allowing the cell to remember, recognize, and clear infections. In this study, the homology of CRISPRs sequence in BIMs (bacteriophage-insensitive mutants) of Streptococcus thermophilus St-I were analyzed. Secondary structures of the repeats and the PAMs (protospacer-associated motif) of each CRISPR locus were also predicted. Results showed that CRISPR1 has 27 repeat-spacer units, 5 of them had duplicates; CRISPR2 has one repeat-spacer unit; CRISPR3 has 28 repeat-spacer units. Only BIM1 had a new spacer acquisition in CRISPR3, while BIM2 and BIM3 had no new spacers' insertion, thus indicating that while most CRISPR1 were more active than CRISPR3, new spacer acquisition occurred just in CRSPR3 in some situations. These findings will help establish the foundation for the study of CRSPR-Cas systems in lactic acid bacteria.
Li, Xu; Gao, Min; Choi, Jong Min; Kim, Beom-Jun; Zhou, Mao-Tian; Chen, Zhen; Jain, Antrix N; Jung, Sung Yun; Yuan, Jingsong; Wang, Wenqi; Wang, Yi; Chen, Junjie
2017-04-01
Neurofibromin (NF1) is a well known tumor suppressor that is commonly mutated in cancer patients. It physically interacts with RAS and negatively regulates RAS GTPase activity. Despite the importance of NF1 in cancer, a high quality endogenous NF1 interactome has yet to be established. In this study, we combined c lustered, r egularly i nterspaced s hort p alindromic r epeats (CRISPR)/Cas9-mediated gene knock-out technology with affinity purification using antibodies against endogenous proteins, followed by mass spectrometry analysis, to sensitively and accurately detect NF1 protein-protein interactions in unaltered in vivo settings. Using this system, we analyzed endogenous NF1-associated protein complexes and identified 49 high-confidence candidate interaction proteins, including RAS and other functionally relevant proteins. Through functional validation, we found that NF1 negatively regulates mechanistic target of rapamycin signaling (mTOR) in a LAMTOR1-dependent manner. In addition, the cell growth and survival of NF1-deficient cells have become dependent on hyperactivation of the mTOR pathway, and the tumorigenic properties of these cells have become dependent on LAMTOR1. Taken together, our findings may provide novel insights into therapeutic approaches targeting NF1-deficient tumors. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Gawryszewska, Iwona; Malinowska, Katarzyna; Kuch, Alicja; Chrobak-Chmiel, Dorota; Trokenheim, Lucja Laniewska-; Hryniewicz, Waleria; Sadowy, Ewa
2017-03-01
Enterococcus faecalis represents an important factor of hospital-associated infections (HAIs). The knowledge on its evolution from a commensal to an opportunistic pathogen is still limited; thus, we performed a study to characterise distribution of factors that may contribute to this adaptation. Using a collection obtained from various settings (hospitalised patients, community carriers, animals, fresh food, sewage, water), we investigated differences in antimicrobial susceptibility, distribution of antimicrobial resistance genes, virulence-associated determinants and phenotypes, and CRISPR loci in the context of the clonal relatedness of isolates. Bayesian Analysis of Population Structure revealed the presence of three major groups; two subgroups comprised almost exclusively HAI isolates, belonging to previously proposed enterococcal high-risk clonal complexes (HiRECCs) 6 and 28. Isolates of these two subgroups were significantly enriched in antimicrobial resistance genes, presumably produced a polysaccharide capsule and often carried the aggregation substance asa1; distribution of other virulence-associated genes, such as esp and cyl, formation of a biofilm and gelatinase production were more variable. Moreover, both subgroups showed a low prevalence of CRISPR-Cas 1 and 3 and presence of small CRISPR2 variants. Our study confirms the importance of HiRECCs in the population of E. faecalis and their confinement to the hospital settings. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
2017-06-30
of the crRNA base pairs with tar- get DNA, whereas the 3’ end forms a double- stranded stem with the tra- crRNA to facilitate Cas9 recruitment...or y Ping Gong June 2017 Approved for public release; distribution is unlimited. The U.S. Army Engineer Research and Development...Gong Environmental Laboratory U.S. Army Engineer Research and Development Center 3909 Halls Ferry Road Vicksburg, MS 39180 Final report
Schmid-Burgk, Jonathan L; Chauhan, Dhruv; Schmidt, Tobias; Ebert, Thomas S; Reinhardt, Julia; Endl, Elmar; Hornung, Veit
2016-01-01
Inflammasomes are high molecular weight protein complexes that assemble in the cytosol upon pathogen encounter. This results in caspase-1-dependent pro-inflammatory cytokine maturation, as well as a special type of cell death, known as pyroptosis. The Nlrp3 inflammasome plays a pivotal role in pathogen defense, but at the same time, its activity has also been implicated in many common sterile inflammatory conditions. To this effect, several studies have identified Nlrp3 inflammasome engagement in a number of common human diseases such as atherosclerosis, type 2 diabetes, Alzheimer disease, or gout. Although it has been shown that known Nlrp3 stimuli converge on potassium ion efflux upstream of Nlrp3 activation, the exact molecular mechanism of Nlrp3 activation remains elusive. Here, we describe a genome-wide CRISPR/Cas9 screen in immortalized mouse macrophages aiming at the unbiased identification of gene products involved in Nlrp3 inflammasome activation. We employed a FACS-based screen for Nlrp3-dependent cell death, using the ionophoric compound nigericin as a potassium efflux-inducing stimulus. Using a genome-wide guide RNA (gRNA) library, we found that targeting Nek7 rescued macrophages from nigericin-induced lethality. Subsequent studies revealed that murine macrophages deficient in Nek7 displayed a largely blunted Nlrp3 inflammasome response, whereas Aim2-mediated inflammasome activation proved to be fully intact. Although the mechanism of Nek7 functioning upstream of Nlrp3 yet remains elusive, these studies provide a first genetic handle of a component that specifically functions upstream of Nlrp3. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Directory of Open Access Journals (Sweden)
Settu Sridhar
Full Text Available The analyses of 3967 representative proteins selected from the Protein Data Bank revealed the presence of 2803 pentapeptide and large palindrome sequences with known secondary structure conformation. These represent 2014 unique palindrome sequences. 60% palindromes are not associated with any regular secondary structure and 28% are in helix conformation, 11% in strand conformation and 1% in the coil conformation. The average solvent accessibility values are in the range between 0-155.28 Å2 suggesting that the palindromes in proteins can be either buried, exposed to the solvent or share an intermittent property. The number of residue neighborhood contacts defined by interactions ≤ 3.2 Ǻ is in the range between 0-29 residues. Palindromes of the same length in helix, strand and coil conformation are associated with different amino acid residue preferences at the individual positions. Nearly, 20% palindromes interact with catalytic/active site residues, ligand or metal ions in proteins and may therefore be important for function in the corresponding protein. The average hydrophobicity values for the pentapeptide and large palindromes range between -4.3 to +4.32 and the number of palindromes is almost equally distributed between the negative and positive hydrophobicity values. The palindromes represent 107 different protein families and the hydrolases, transferases, oxidoreductases and lyases contain relatively large number of palindromes.
The JET vacuum interspace system
International Nuclear Information System (INIS)
Orchard, J.; Scales, S.
1999-01-01
In the past JET has suffered from a number of vacuum leaks on components such as bellows, windows and feedthroughs due, in part, to the adverse conditions, including high mechanical forces, which may prevail during plasma operation. Therefore before the recent Tritium experiments on JET it was deemed prudent to manufacture and install items with a secondary containment or interspace in order to minimise the effect of failure of the primary vacuum barrier on both the leak integrity of the machine and the outcome of the experiments. This paper describes the philosophy, logistics, method and implementation of an integrated connection and monitoring system on the 330 interspaces currently in position on the JET machine. Using the JET leak database comparisons are drawn of leak failure rates of the components allied to the number of operational hours, prior to the system being present and after installation and commissioning, and the case of detection compared to the previous situation. An argument is also presented on the feasibility and adaptability of this system to any large complex machine and the benefits to be obtained in reduction of leaks and operational down time. (author)
Palindromic widths of nilpotent and wreath products
Indian Academy of Sciences (India)
Palindromic width; commutator width; wreath products; nilpotent product. 2000 Mathematics ... An algorithm of the computation of the commutator length in free non-abelian .... It is clear that A(1)B = A × B is the direct sum. Let us list some ...
Singular continuous spectrum for palindromic Schroedinger operators
International Nuclear Information System (INIS)
Hof, A.; Knill, O.; Simon, B.
1995-01-01
We give new examples of discrete Schroedinger operators with potentials taking finitely many values that have purely singular continuous spectrum. If the hull X of the potential is strictly ergodic, then the existence of just one potential x in X for which the operator has no eigenvalues implies that there is a generic set in X for which the operator has purely singular continuous spectrum. A sufficient condition for the existence of such an x is that there is a z element of X that contains arbitrarily long palindromes. Thus we can define a large class of primitive substitutions for which the operators are purely singularly continuous for a generic subset in X. The class includes well-known substitutions like Fibonacci, Thue-Morse, Period Doubling, binary non-Pisot and ternary non-Pisot. We also show that the operator has no absolutely continuous spectrum for all x element of X if X derives from a primitive substitution. For potentials defined by circle maps, x n =l J (θ 0 +nα), we show that the operator has purely singular continuous spectrum for a generic subset in X for all irrational α and every half-open interval J. (orig.)
In-service inspection in the Superphenix 1 vessels interspace
International Nuclear Information System (INIS)
Asty, M.; Saglio, R.
1983-03-01
The design of Superphenix 1 reactor vessels allows their in-service inspection. A self-propelling engine, the MIR, has been concieved for this need: it can do a visual and ultrasonic inspection. The MIR can move in the whole vessels interspace. The operating conditions are specified and the principle characteristics of the MIR engine are presented [fr
Schroedinger operators with Rudin-Shapiro potentials are not palindromic
International Nuclear Information System (INIS)
Allouche, J.
1997-01-01
We prove a conjecture of A. Hof, O. Knill and B. Simon [Commun. Math. Phys. 174, 149 endash 159 (1995)] by showing that the Rudin-Shapiro sequence is not palindromic, i.e., does not contain arbitrarily long palindromes. We prove actually this property for all paperfolding sequences and all Rudin-Shapiro sequences deduced from paperfolding sequences. As a consequence and as guessed by the above authors, their method cannot be used for establishing that discrete Schroedinger operators with Rudin-Shapiro potentials have a purely singular continuous spectrum. copyright 1997 American Institute of Physics
An algorithm to find all palindromic sequences in proteins
Indian Academy of Sciences (India)
2013-01-20
Jan 20, 2013 ... 1976; Karrer and Gall 1976; Vogt and Braun 1976) and (iii) in the formation of hairpin loops in the newly transcribed RNA. Palindromic sequences are observed in various classes of proteins like histones (Cheng et al. 1989), prion proteins (Sulkowski 1992; Kazim 1993),. DNA-binding proteins (Suzuki 1992; ...
Trapping of palindromic ligands within native transthyretin prevents amyloid formation
Kolstoe, Simon E.; Mangione, Palma P.; Bellotti, Vittorio; Taylor, Graham W.; Tennent, Glenys A.; Deroo, Stéphanie; Morrison, Angus J.; Cobb, Alexander J. A.; Coyne, Anthony; McCammon, Margaret G.; Warner, Timothy D.; Mitchell, Jane; Gill, Raj; Smith, Martin D.; Ley, Steven V.
2010-01-01
Transthyretin (TTR) amyloidosis is a fatal disease for which new therapeutic approaches are urgently needed. We have designed two palindromic ligands, 2,2'-(4,4'-(heptane-1,7-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (mds84) and 2,2'-(4,4'-(undecane-1,11-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (4ajm15), that are rapidly bound by native wild-type TTR in whole serum and even more avidly by amyloidogenic TTR variants. One to one...
International Nuclear Information System (INIS)
Caldwell, M.M.; Eissenstat, D.M.; Richards, J.H.; Allen, M.F.
1985-01-01
Two species of Agropyron grass differed strikingly in their capacity to compete for phosphate in soil interspaces shared with a common competitor, the sagebrush Artemisia tridentata. Of the total phosphorus-32 and -33 absorbed by Artemisia, 86% was from the interspace shared with Agropyron spicatum and only 14% from that shared with Agropyron desertorum. Actively absorbing mycorrhizal roots of Agropyron and Artemisia were present in both interspaces, where competition for the labeled phosphate occurred. The results have important implications about the way in which plants compete for resources below ground in both natural plant communities and agricultural intercropping systems
Characteristics of palindromic sequences in DNA of the sea urchin Stronglyocentrotus intermedius
International Nuclear Information System (INIS)
Brykov, V.A.; Kukhlevskii, A.D.
1986-01-01
The fraction of palindromic sequences in the nuclear DNA of the sea urchin S. intermedius was characterized. Using chromatography on hydroxyapatite and treatment with S1 nuclease, it was shown that the fraction of palindromic sequences more than doubles when the sodium concentration in solution is increased or the temperature of reassociation is lowered. The increase is due to the involvement of inverted repeats in reassociation, which are characterized by a substantial nonhomologous character and/or the presence of an extended intervening DNA sequence. It was found by the method of reassociation of a nicked palindrome fraction with an excess of total homologous DNA that most of the inverted repeats in the sea urchin genome are unique sequences. The complexity of the palindrome fraction was estimated at 8.2 x 10 7 nucleotide pairs, and the number of palindromes per haploid genome ∼ 500,000
Palindromic nucleotide analysis in human T cell receptor rearrangements.
Directory of Open Access Journals (Sweden)
Santosh K Srivastava
Full Text Available Diversity of T cell receptor (TCR genes is primarily generated by nucleotide insertions upon rearrangement from their germ line-encoded V, D and J segments. Nucleotide insertions at V-D and D-J junctions are random, but some small subsets of these insertions are exceptional, in that one to three base pairs inversely repeat the sequence of the germline DNA. These short complementary palindromic sequences are called P nucleotides. We apply the ImmunoSeq deep-sequencing assay to the third complementarity determining region (CDR3 of the β chain of T cell receptors, and use the resulting data to study P nucleotides in the repertoire of naïve and memory CD8(+ and CD4(+ T cells. We estimate P nucleotide distributions in a cross section of healthy adults and different T cell subtypes. We show that P nucleotide frequency in all T cell subtypes ranges from 1% to 2%, and that the distribution is highly biased with respect to the coding end of the gene segment. Classification of observed palindromic sequences into P nucleotides using a maximum conditional probability model shows that single base P nucleotides are very rare in VDJ recombination; P nucleotides are primarily two bases long. To explore the role of P nucleotides in thymic selection, we compare P nucleotides in productive and non-productive sequences of CD8(+ naïve T cells. The naïve CD8(+ T cell clones with P nucleotides are more highly expanded.
Design principles for nuclease-deficient CRISPR-based transcriptional regulators
DEFF Research Database (Denmark)
Jensen, Michael K.
2018-01-01
The engineering of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated proteins (Cas) continues to expand the toolkit available for genome editing, reprogramming gene regulation, genome visualization, and epigenetic studies of living organisms. In this review the ...
T.R. Sampson (Timothy); B.A. Napier (Brooke); M.R. Schroeder (Max); J. Zhao (Jingshi); R.P.L. Louwen (Rogier); C.-Y. Chin (Chui-Yoke); H.K. Ratner (Hannah); A.C. Llewellyn (Anna); C.L. Jones (Crystal); H. Laroui (Hamed); D. Merlin (Didier); P. Zhou (Pei); H.P. Endtz (Hubert); D.S. Weiss (David)
2014-01-01
textabstractClustered, regularly interspaced, short palindromic repeats-CRISPR associated (CRISPR-Cas) systems defend bacteria against foreign nucleic acids, such as during bacteriophage infection and transformation, processes which cause envelope stress. It is unclear if these machineries enhance
Unravelling the structural and mechanistic basis of CRISPR-Cas systems
Oost, van der J.; Westra, E.R.; Jackson, R.N.; Wiedenheft, B.
2014-01-01
Bacteria and archaea have evolved sophisticated adaptive immune systems, known as CRISPR–Cas (clustered regularly interspaced short palindromic repeats–CRISPR-associated proteins) systems, which target and inactivate invading viruses and plasmids. Immunity is acquired by integrating short fragments
B.M. Pearson (Bruce M.); R.P.L. Louwen (Rogier); P. van Baarlen (Peter); A.H.M. van Vliet (Arnoud)
2015-01-01
textabstractCRISPR (clustered regularly interspaced palindromic repeats)-Cas (CRISPR-associated) systems are sequence-specific adaptive defenses against phages and plasmidswhich are widespread in prokaryotes. Herewehave studiedwhether phylogenetic relatedness or sharing of environmental niches
CRISPR and the Rebirth of Synthetic Biology
Heidari, Raheleh; Shaw, David Martin; Elger, Bernice Simone
Emergence of novel genome engineering technologies such as clustered regularly interspaced short palindromic repeat (CRISPR) has refocused attention on unresolved ethical complications of synthetic biology. Biosecurity concerns, deontological issues and human right aspects of genome editing have
Structural basis for CRISPR RNA-guided DNA recognition by Cascade
Jore, M.M.; Lundgren, N.M.J.; Duijn, van E.; Bultema, J.B.; Westra, E.R.; Oost, van der J.; Brouns, S.J.J.; Beijer, M.R.
2011-01-01
The CRISPR (clustered regularly interspaced short palindromic repeats) immune system in prokaryotes uses small guide RNAs to neutralize invading viruses and plasmids. In Escherichia coli, immunity depends on a ribonucleoprotein complex called Cascade. Here we present the composition and
Westra, E.R.; Semenova, E.; Datsenko, K.A.; Jackson, R.N.; Wiedenheft, B.; Severinov, K.; Brouns, S.J.J.
2013-01-01
Discriminating self and non-self is a universal requirement of immune systems. Adaptive immune systems in prokaryotes are centered around repetitive loci called CRISPRs (clustered regularly interspaced short palindromic repeat), into which invader DNA fragments are incorporated. CRISPR transcripts
Pearson, Bruce M.; Louwen, Rogier; Baarlen, Van Peter; Vliet, Van Arnoud H.M.
2015-01-01
CRISPR (clustered regularly interspaced palindromic repeats)-Cas (CRISPR-associated) systems are sequence-specific adaptive defenses against phages and plasmidswhich are widespread in prokaryotes. Herewehave studiedwhether phylogenetic relatedness or sharing of environmental niches affects the
Multiplexed CRISPR/Cas9 Genome Editing and Gene Regulation Using Csy4 in Saccharomyces cerevisiae
DEFF Research Database (Denmark)
Ferreira, Raphael; Skrekas, Christos; Nielsen, Jens
2018-01-01
Clustered regularly interspaced short palindromic repeats (CRISPR) technology has greatly accelerated the field of strain engineering. However, insufficient efforts have been made toward developing robust multiplexing tools in Saccharomyces cerevisiae. Here, we exploit the RNA processing capacity...
Structural basis for CRISPR RNA-guided DNA recognition by Cascade
Jore, Matthijs M.; Lundgren, Magnus; van Duijn, Esther; Bultema, Jelle B.; Westra, Edze R.; Waghmare, Sakharam P.; Wiedenheft, Blake; Pul, Uemit; Wurm, Reinhild; Wagner, Rolf; Beijer, Marieke R.; Barendregt, Arjan; Zhou, Kaihong; Snijders, Ambrosius P. L.; Dickman, Mark J.; Doudna, Jennifer A.; Boekema, Egbert J.; Heck, Albert J. R.; van der Oost, John; Brouns, Stan J. J.; Pul, Ümit
The CRISPR (clustered regularly interspaced short palindromic repeats) immune system in prokaryotes uses small guide RNAs to neutralize invading viruses and plasmids. In Escherichia coli, immunity depends on a ribonucleoprotein complex called Cascade. Here we present the composition and
Targeted Genome Regulation and Editing in Plants
Piatek, Agnieszka Anna
2016-01-01
for bioengineering applications. However, the TALE system is limited by the requirement to re-engineer one or two proteins for each new target sequence. Recently, the clustered regularly interspaced palindromic repeats (CRISPR)/ CRISPR associated 9 (Cas9) has been
Directory of Open Access Journals (Sweden)
Fei Qi
2007-10-01
Full Text Available Abstract Background In idiopathic scoliosis patients, after anterior spinal fusion and instrumentation, the discs (interspace angle between the lowest instrumented vertebra (LIV and the next caudal vertebra became more wedged. We reviewed these patients and analyzed the changes of the angle. Methods By reviewing the medical records and roentgenograms of adolescent idiopathic scoliosis patients underwent anterior spinal fusion and instrumentation, Cobb angle of the curve, correction rate, coronal balance, LIV rotation, interspace angle were measured and analyzed. Results There were total 30 patients included. The mean coronal Cobb angle of the main curve (thoracolumbar/lumbar curve before and after surgery were 48.9° and 11.7°, respectively, with an average correction rate of 76.1%. The average rotation of LIV before surgery was 2.1 degree, and was improved to 1.2 degree after surgery. The interspace angle before surgery, on convex side-bending films, after surgery, at final follow up were 3.2°, -2.3°, 1.8° and 4.9°, respectively. The difference between the interspace angle after surgery and that preoperatively was not significant (P = 0.261, while the interspace angle at final follow-up became larger than that after surgery, and the difference was significant(P = 0.012. The interspace angle after surgery was correlated with that on convex side-bending films (r = 0.418, P = 0.022, and the interspace angle at final follow-up was correlated with that after surgery (r = 0.625, P = 0.000. There was significant correlation between the loss of the interspace angle and the loss of coronal Cobb angle of the main curve during follow-up(r = 0.483, P = 0.007. Conclusion The interspace angle could be improved after anterior correction and instrumentation surgery, but it became larger during follow-up. The loss of the interspace angle was correlated with the loss of coronal Cobb angle of the main curve during follow-up.
DEFF Research Database (Denmark)
Shah, Shiraz Ali; Hansen, Niels R; Garrett, Roger A
2009-01-01
Transcripts from spacer sequences within chromosomal repeat clusters [CRISPRs (clusters of regularly interspaced palindromic repeats)] from archaea have been implicated in inhibiting or regulating the propagation of archaeal viruses and plasmids. For the crenarchaeal thermoacidophiles, the chromo......Transcripts from spacer sequences within chromosomal repeat clusters [CRISPRs (clusters of regularly interspaced palindromic repeats)] from archaea have been implicated in inhibiting or regulating the propagation of archaeal viruses and plasmids. For the crenarchaeal thermoacidophiles...
DEFF Research Database (Denmark)
Hansen, Lars Kai; Rasmussen, Carl Edward; Svarer, C.
1994-01-01
Regularization, e.g., in the form of weight decay, is important for training and optimization of neural network architectures. In this work the authors provide a tool based on asymptotic sampling theory, for iterative estimation of weight decay parameters. The basic idea is to do a gradient desce...
Trapping of palindromic ligands within native transthyretin prevents amyloid formation
Kolstoe, Simon E.; Mangione, Palma P.; Bellotti, Vittorio; Taylor, Graham W.; Tennent, Glenys A.; Deroo, Stéphanie; Morrison, Angus J.; Cobb, Alexander J. A.; Coyne, Anthony; McCammon, Margaret G.; Warner, Timothy D.; Mitchell, Jane; Gill, Raj; Smith, Martin D.; Ley, Steven V.; Robinson, Carol V.; Wood, Stephen P.; Pepys, Mark B.
2010-01-01
Transthyretin (TTR) amyloidosis is a fatal disease for which new therapeutic approaches are urgently needed. We have designed two palindromic ligands, 2,2'-(4,4'-(heptane-1,7-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (mds84) and 2,2'-(4,4'-(undecane-1,11-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (4ajm15), that are rapidly bound by native wild-type TTR in whole serum and even more avidly by amyloidogenic TTR variants. One to one stoichiometry, demonstrable in solution and by MS, was confirmed by X-ray crystallographic analysis showing simultaneous occupation of both T4 binding sites in each tetrameric TTR molecule by the pair of ligand head groups. Ligand binding by native TTR was irreversible under physiological conditions, and it stabilized the tetrameric assembly and inhibited amyloidogenic aggregation more potently than other known ligands. These superstabilizers are orally bioavailable and exhibit low inhibitory activity against cyclooxygenase (COX). They offer a promising platform for development of drugs to treat and prevent TTR amyloidosis. PMID:21059958
Interspace modification of titania-nanorod arrays for efficient mesoscopic perovskite solar cells
International Nuclear Information System (INIS)
Chen, Peng; Jin, Zhixin; Wang, Yinglin; Wang, Meiqi; Chen, Shixin; Zhang, Yang; Wang, Lingling; Zhang, Xintong; Liu, Yichun
2017-01-01
Highlights: • The fabrication of perovskite solar cells utilizing TiO_2 NR arrays. • Investigation of the interspace effect of TiO_2 NR on perovskite layer. • Understanding of the balance between perovskite capping layer and pore filling. - Abstract: Morphology of electron transport layers (ETLs) has an important influence on the device architecture and electronic processes of mesostructured solar cells. In this work, we thoroughly investigated the effect of the interspace of TiO_2 nanorod (NR) arrays on the photovoltaic performance of the perovskite solar cells (PSCs). Along with the interspace in TiO_2-NR arrays increasing, the thickness as well as the crystal size of perovskite capping layer are reduced accordingly, and the filling of perovskite in the channel becomes incomplete. Electrochemical impedance spectroscopy measurements reveal that this variation of perovskite absorber layer, induced by interspace of TiO_2 NR arrays, causes the change of charge recombination process at the TiO_2/perovskite interface, suggesting that a balance between capping layer and the perovskite filling is critical to obtain high charge collection efficiency of PSCs. A power conversion efficiency of 10.3% could be achieved through careful optimization of interspace in TiO_2-NR arrays. Our research will shed light on the morphology control of ETLs with 1D structure for heterojunction solar cells fabricated by solution-deposited method.
Interspace modification of titania-nanorod arrays for efficient mesoscopic perovskite solar cells
Energy Technology Data Exchange (ETDEWEB)
Chen, Peng; Jin, Zhixin; Wang, Yinglin, E-mail: wangyl100@nenu.edu.cn; Wang, Meiqi; Chen, Shixin; Zhang, Yang; Wang, Lingling; Zhang, Xintong, E-mail: xtzhang@nenu.edu.cn; Liu, Yichun, E-mail: ycliu@nenu.edu.cn
2017-04-30
Highlights: • The fabrication of perovskite solar cells utilizing TiO{sub 2} NR arrays. • Investigation of the interspace effect of TiO{sub 2} NR on perovskite layer. • Understanding of the balance between perovskite capping layer and pore filling. - Abstract: Morphology of electron transport layers (ETLs) has an important influence on the device architecture and electronic processes of mesostructured solar cells. In this work, we thoroughly investigated the effect of the interspace of TiO{sub 2} nanorod (NR) arrays on the photovoltaic performance of the perovskite solar cells (PSCs). Along with the interspace in TiO{sub 2}-NR arrays increasing, the thickness as well as the crystal size of perovskite capping layer are reduced accordingly, and the filling of perovskite in the channel becomes incomplete. Electrochemical impedance spectroscopy measurements reveal that this variation of perovskite absorber layer, induced by interspace of TiO{sub 2} NR arrays, causes the change of charge recombination process at the TiO{sub 2}/perovskite interface, suggesting that a balance between capping layer and the perovskite filling is critical to obtain high charge collection efficiency of PSCs. A power conversion efficiency of 10.3% could be achieved through careful optimization of interspace in TiO{sub 2}-NR arrays. Our research will shed light on the morphology control of ETLs with 1D structure for heterojunction solar cells fabricated by solution-deposited method.
Directory of Open Access Journals (Sweden)
Timothy R. Larsen
2012-01-01
Full Text Available Palindromic rheumatism is a rare disease associated with systemic inflammation. Negative or constrictive coronary artery remodeling is typically not seen until the 7th or 8th decade of life. We report a case of a young female with palindromic rheumatism who suffered a non-ST segment elevation myocardial infarction secondary to a flow-limiting lesion that demonstrated negative remodeling by intravascular ultrasound (IVUS.
Interspace modification of titania-nanorod arrays for efficient mesoscopic perovskite solar cells
Chen, Peng; Jin, Zhixin; Wang, Yinglin; Wang, Meiqi; Chen, Shixin; Zhang, Yang; Wang, Lingling; Zhang, Xintong; Liu, Yichun
2017-04-01
Morphology of electron transport layers (ETLs) has an important influence on the device architecture and electronic processes of mesostructured solar cells. In this work, we thoroughly investigated the effect of the interspace of TiO2 nanorod (NR) arrays on the photovoltaic performance of the perovskite solar cells (PSCs). Along with the interspace in TiO2-NR arrays increasing, the thickness as well as the crystal size of perovskite capping layer are reduced accordingly, and the filling of perovskite in the channel becomes incomplete. Electrochemical impedance spectroscopy measurements reveal that this variation of perovskite absorber layer, induced by interspace of TiO2 NR arrays, causes the change of charge recombination process at the TiO2/perovskite interface, suggesting that a balance between capping layer and the perovskite filling is critical to obtain high charge collection efficiency of PSCs. A power conversion efficiency of 10.3% could be achieved through careful optimization of interspace in TiO2-NR arrays. Our research will shed light on the morphology control of ETLs with 1D structure for heterojunction solar cells fabricated by solution-deposited method.
Energy Technology Data Exchange (ETDEWEB)
Shurvinton, C.E.; Stahl, M.M.; Stahl, F.W.
1987-03-01
A large palindrome carried by phage lambda has been shown to prevent growth of the phage on a rec/sup +/ strain of Escherichia coli. The phage do form plaques on recBC sbcB strains, but the palindrome is not stable - deletions that either destroy the palindrome or diminish its size overgrow the original engineered palindrome-containing phage. The authors have prepared stocks of lambda carrying a palindrome that is 2 x 4200 base pairs long. lambda phage were density labeled by UV induction of lysogens grown in minimal medium containing (/sup 13/C) glucose and /sup 15/NH/sub 4/Cl. These phage stocks are produced by induction of a lysogen in which the two halves of the palindrome are stored at opposite ends of the prophage and are of sufficient titer (10/sup 9/ phage per ml) to enable one-step growth experiments with replication-blocked phage. They find that the large palindrome as well as a lesser palindrome of 2 x 265 base pairs are recovered intact among particles carrying unreplicated chromosomes following such an infection of a rec/sup +/ host. they propose that DNA replication drives the extrusion of palindromic sequences in vivo, forming secondary structures that are substrates for the recBC and sbcB gene products.
New insights into the nanometer-scaled cell-surface interspace by cell-sensor measurements
International Nuclear Information System (INIS)
Lehmann, Mirko; Baumann, Werner
2005-01-01
The culture of adherent cells on solid surfaces is an established in vitro method, and the adhesion process of a cell is considered as an important trigger for many cellular processes (e.g., polarity and tumor genesis). However, not all of the eliciting biochemical or biophysical reactions are yet understood. Interestingly, there are not much experimental data about the impact that the interspace between an adherent cell and the (solid) substrate has on the cell's behavior. This interspace is mainly built by the basolateral side of epithelial cells and the substrate. This paper gives some new results of non-invasive and non-optical measurements in the interspace. The measurements were made with silicon cell-sensor hybrids. Measurements of acidification, adhesion, and respiration are analyzed in view of the situation in the interspace. The results show that, in general, the release of an ion or molecule on the basolateral side can have much more influence on the biophysical situation than a release of an ion or molecule on the apical side. In particular, the apical acidification (i.e., amount of extruded protons) of, e.g., epithelial tumor cells is several orders of magnitude higher than the basolateral acidification. These experimental results are a simple consequence of the fact that the basolateral volume of the interspace is several orders of magnitudes smaller than the apical volume. These results have the following consequences for the cell adhesion:a)static situation: if a cell is already adhered to a solid substrate, the basolateral and apical release and uptake of molecules have to be considered in a very differentiated way; b)dynamic situation: if the cell is adhering to the substrate, the then built basolateral side changes in a much stronger way than the apical side. This effect is here discussed as a possible eliciting and general mechanism for essential intracellular changes
National Research Council Canada - National Science Library
Robbins, Ronny C
2004-01-01
.... This is similar to words such as STOP which when flipped left right gives the new word POTS. Emordnilap is palindrome spelled backwards. This paper explores the use of MATLAB algorithms in the rapid detection and embedding of palindrome and emordnilap electronic watermarks in simulated chemical and biological Image Data.
UNFOLDED REGULAR AND SEMI-REGULAR POLYHEDRA
Directory of Open Access Journals (Sweden)
IONIŢĂ Elena
2015-06-01
Full Text Available This paper proposes a presentation unfolding regular and semi-regular polyhedra. Regular polyhedra are convex polyhedra whose faces are regular and equal polygons, with the same number of sides, and whose polyhedral angles are also regular and equal. Semi-regular polyhedra are convex polyhedra with regular polygon faces, several types and equal solid angles of the same type. A net of a polyhedron is a collection of edges in the plane which are the unfolded edges of the solid. Modeling and unfolding Platonic and Arhimediene polyhedra will be using 3dsMAX program. This paper is intended as an example of descriptive geometry applications.
Mre11-Sae2 and RPA Collaborate to Prevent Palindromic Gene Amplification.
Deng, Sarah K; Yin, Yi; Petes, Thomas D; Symington, Lorraine S
2015-11-05
Foldback priming at DNA double-stranded breaks is one mechanism proposed to initiate palindromic gene amplification, a common feature of cancer cells. Here, we show that small (5-9 bp) inverted repeats drive the formation of large palindromic duplications, the major class of chromosomal rearrangements recovered from yeast cells lacking Sae2 or the Mre11 nuclease. RPA dysfunction increased the frequency of palindromic duplications in Sae2 or Mre11 nuclease-deficient cells by ∼ 1,000-fold, consistent with intra-strand annealing to create a hairpin-capped chromosome that is subsequently replicated to form a dicentric isochromosome. The palindromic duplications were frequently associated with duplication of a second chromosome region bounded by a repeated sequence and a telomere, suggesting the dicentric chromosome breaks and repairs by recombination between dispersed repeats to acquire a telomere. We propose secondary structures within single-stranded DNA are potent instigators of genome instability, and RPA and Mre11-Sae2 play important roles in preventing their formation and propagation, respectively. Copyright © 2015 Elsevier Inc. All rights reserved.
Coordinate-invariant regularization
International Nuclear Information System (INIS)
Halpern, M.B.
1987-01-01
A general phase-space framework for coordinate-invariant regularization is given. The development is geometric, with all regularization contained in regularized DeWitt Superstructures on field deformations. Parallel development of invariant coordinate-space regularization is obtained by regularized functional integration of the momenta. As representative examples of the general formulation, the regularized general non-linear sigma model and regularized quantum gravity are discussed. copyright 1987 Academic Press, Inc
Abundance and distribution of the highly iterated palindrome 1 (HIP1) among prokaryotes
Delaye, Luis; Moya, Andrés
2011-01-01
We have studied the abundance and phylogenetic distribution of the Highly Iterated Palindrome 1 (HIP1) among sequenced prokaryotic genomes. We show that an overrepresentation of HIP1 is exclusive of some lineages of cyanobacteria, and that this abundance was gained only once during evolution and was subsequently lost in the lineage leading to marine pico-cyanobacteria. We show that among cyanobacterial protein sequences with annotated Pfam domains, only OpcA (glucose 6-phosphate dehydrogenase...
Palindromic Molecule Beacon-Based Cascade Amplification for Colorimetric Detection of Cancer Genes.
Shen, Zhi-Fa; Li, Feng; Jiang, Yi-Fan; Chen, Chang; Xu, Huo; Li, Cong-Cong; Yang, Zhe; Wu, Zai-Sheng
2018-03-06
A highly sensitive and selective colorimetric assay based on a multifunctional molecular beacon with palindromic tail (PMB) was proposed for the detection of target p53 gene. The PMB probe can serve as recognition element, primer, and polymerization template and contains a nicking site and a C-rich region complementary to a DNAzyme. In the presence of target DNA, the hairpin of PMB is opened, and the released palindromic tails intermolecularly hybridize with each other, triggering the autonomous polymerization/nicking/displacement cycles. Although only one type of probe is involved, the system can execute triple and continuous polymerization strand displacement amplifications, generating large amounts of G-quadruplex fragments. These G-rich fragments can bind to hemin and form the DNAzymes that possess the catalytic activity similar to horseradish peroxidase, catalyzing the oxidation of ABTS by H 2 O 2 and producing the colorimetric signal. Utilizing the newly proposed sensing system, target DNA can be detected down to 10 pM with a linear response range from 10 pM to 200 nM, and mutant target DNAs are able to be distinguished even by the naked eye. The desirable detection sensitivity, high specificity, and operation convenience without any separation step and chemical modification demonstrate that the palindromic molecular beacon holds the potential for detecting and monitoring a variety of nucleic acid-related biomarkers.
The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1.
Diccianni, M B; Imagawa, M; Muramatsu, M
1992-01-01
Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lac...
van Dam, Edwin R.; Koolen, Jack H.; Tanaka, Hajime
2016-01-01
This is a survey of distance-regular graphs. We present an introduction to distance-regular graphs for the reader who is unfamiliar with the subject, and then give an overview of some developments in the area of distance-regular graphs since the monograph 'BCN'[Brouwer, A.E., Cohen, A.M., Neumaier,
Nijholt, Antinus
1980-01-01
Culik II and Cogen introduced the class of LR-regular grammars, an extension of the LR(k) grammars. In this paper we consider an analogous extension of the LL(k) grammars called the LL-regular grammars. The relation of this class of grammars to other classes of grammars will be shown. Any LL-regular
Regular Expression Pocket Reference
Stubblebine, Tony
2007-01-01
This handy little book offers programmers a complete overview of the syntax and semantics of regular expressions that are at the heart of every text-processing application. Ideal as a quick reference, Regular Expression Pocket Reference covers the regular expression APIs for Perl 5.8, Ruby (including some upcoming 1.9 features), Java, PHP, .NET and C#, Python, vi, JavaScript, and the PCRE regular expression libraries. This concise and easy-to-use reference puts a very powerful tool for manipulating text and data right at your fingertips. Composed of a mixture of symbols and text, regular exp
Giangaspero, Massimo; Harasawa, Ryô
2007-12-01
The palindromic nucleotide substitutions (PNS) at the three variable loci (V1, V2 and V3) in the 5' untranslated region (UTR) of Pestivirus RNA have been considered for taxonomical segregation of species, through the evaluation of 430 genomic sequences. On the basis of qualitative and quantitative secondary structure characteristics, six species have been identified: Bovine viral diarrhea virus 1 (BVDV-1), Bovine viral diarrhea virus 2 (BVDV-2), Classical swine fever virus (CSFV), Border disease virus (BDV), the tentative species Giraffe and a new proposed taxon named Pronghorn. The first step was qualitative and consisted in the characterization of the different positions of the three stems and loops in the 5' UTR sequences of all the strains under consideration belonging to the genus. Secondary structure sequences showing divergent base-pair combinations have been aligned for comparison. Palindromic positions have been characterized according to changes in nucleotide base-pairs identifying low-variable positions (LVP) including base-pairs present in less than 80% of the genus. The second step was quantitative, allowing the identification of genomic groups by clustering the base-pair combinations according to LVP. Relatedness among types was evaluated to identify homogeneous groups. Cross comparisons between types within the genus have been evaluated by computing the divergence percentage thus clarifying borderline and multirelated sequences.
Regularization by External Variables
DEFF Research Database (Denmark)
Bossolini, Elena; Edwards, R.; Glendinning, P. A.
2016-01-01
Regularization was a big topic at the 2016 CRM Intensive Research Program on Advances in Nonsmooth Dynamics. There are many open questions concerning well known kinds of regularization (e.g., by smoothing or hysteresis). Here, we propose a framework for an alternative and important kind of regula......Regularization was a big topic at the 2016 CRM Intensive Research Program on Advances in Nonsmooth Dynamics. There are many open questions concerning well known kinds of regularization (e.g., by smoothing or hysteresis). Here, we propose a framework for an alternative and important kind...
Goyvaerts, Jan
2009-01-01
This cookbook provides more than 100 recipes to help you crunch data and manipulate text with regular expressions. Every programmer can find uses for regular expressions, but their power doesn't come worry-free. Even seasoned users often suffer from poor performance, false positives, false negatives, or perplexing bugs. Regular Expressions Cookbook offers step-by-step instructions for some of the most common tasks involving this tool, with recipes for C#, Java, JavaScript, Perl, PHP, Python, Ruby, and VB.NET. With this book, you will: Understand the basics of regular expressions through a
Regularities of Multifractal Measures
Indian Academy of Sciences (India)
First, we prove the decomposition theorem for the regularities of multifractal Hausdorff measure and packing measure in R R d . This decomposition theorem enables us to split a set into regular and irregular parts, so that we can analyze each separately, and recombine them without affecting density properties. Next, we ...
Stochastic analytic regularization
International Nuclear Information System (INIS)
Alfaro, J.
1984-07-01
Stochastic regularization is reexamined, pointing out a restriction on its use due to a new type of divergence which is not present in the unregulated theory. Furthermore, we introduce a new form of stochastic regularization which permits the use of a minimal subtraction scheme to define the renormalized Green functions. (author)
Sparse structure regularized ranking
Wang, Jim Jing-Yan; Sun, Yijun; Gao, Xin
2014-01-01
Learning ranking scores is critical for the multimedia database retrieval problem. In this paper, we propose a novel ranking score learning algorithm by exploring the sparse structure and using it to regularize ranking scores. To explore the sparse
Regular expression containment
DEFF Research Database (Denmark)
Henglein, Fritz; Nielsen, Lasse
2011-01-01
We present a new sound and complete axiomatization of regular expression containment. It consists of the conventional axiomatiza- tion of concatenation, alternation, empty set and (the singleton set containing) the empty string as an idempotent semiring, the fixed- point rule E* = 1 + E × E......* for Kleene-star, and a general coin- duction rule as the only additional rule. Our axiomatization gives rise to a natural computational inter- pretation of regular expressions as simple types that represent parse trees, and of containment proofs as coercions. This gives the axiom- atization a Curry......-Howard-style constructive interpretation: Con- tainment proofs do not only certify a language-theoretic contain- ment, but, under our computational interpretation, constructively transform a membership proof of a string in one regular expres- sion into a membership proof of the same string in another regular expression. We...
Supersymmetric dimensional regularization
International Nuclear Information System (INIS)
Siegel, W.; Townsend, P.K.; van Nieuwenhuizen, P.
1980-01-01
There is a simple modification of dimension regularization which preserves supersymmetry: dimensional reduction to real D < 4, followed by analytic continuation to complex D. In terms of component fields, this means fixing the ranges of all indices on the fields (and therefore the numbers of Fermi and Bose components). For superfields, it means continuing in the dimensionality of x-space while fixing the dimensionality of theta-space. This regularization procedure allows the simple manipulation of spinor derivatives in supergraph calculations. The resulting rules are: (1) First do all algebra exactly as in D = 4; (2) Then do the momentum integrals as in ordinary dimensional regularization. This regularization procedure needs extra rules before one can say that it is consistent. Such extra rules needed for superconformal anomalies are discussed. Problems associated with renormalizability and higher order loops are also discussed
Regularized maximum correntropy machine
Wang, Jim Jing-Yan; Wang, Yunji; Jing, Bing-Yi; Gao, Xin
2015-01-01
In this paper we investigate the usage of regularized correntropy framework for learning of classifiers from noisy labels. The class label predictors learned by minimizing transitional loss functions are sensitive to the noisy and outlying labels of training samples, because the transitional loss functions are equally applied to all the samples. To solve this problem, we propose to learn the class label predictors by maximizing the correntropy between the predicted labels and the true labels of the training samples, under the regularized Maximum Correntropy Criteria (MCC) framework. Moreover, we regularize the predictor parameter to control the complexity of the predictor. The learning problem is formulated by an objective function considering the parameter regularization and MCC simultaneously. By optimizing the objective function alternately, we develop a novel predictor learning algorithm. The experiments on two challenging pattern classification tasks show that it significantly outperforms the machines with transitional loss functions.
Regularized maximum correntropy machine
Wang, Jim Jing-Yan
2015-02-12
In this paper we investigate the usage of regularized correntropy framework for learning of classifiers from noisy labels. The class label predictors learned by minimizing transitional loss functions are sensitive to the noisy and outlying labels of training samples, because the transitional loss functions are equally applied to all the samples. To solve this problem, we propose to learn the class label predictors by maximizing the correntropy between the predicted labels and the true labels of the training samples, under the regularized Maximum Correntropy Criteria (MCC) framework. Moreover, we regularize the predictor parameter to control the complexity of the predictor. The learning problem is formulated by an objective function considering the parameter regularization and MCC simultaneously. By optimizing the objective function alternately, we develop a novel predictor learning algorithm. The experiments on two challenging pattern classification tasks show that it significantly outperforms the machines with transitional loss functions.
Giangaspero, Massimo; Harasawa, Ryô
2011-06-01
The palindromic nucleotide substitutions (PNS) at the three variable loci (V1, V2 and V3) in the 5'-untranslated region (UTR) of the Pestivirus genome have been considered for taxonomical segregation of the species, through the evaluation of 534 strains. On the basis of qualitative and quantitative secondary structure characteristics, species have been identified within the genus, determining genetic distances between species isolates, clarifying borderline and multirelated sequences, and characterizing and clustering the Pestivirus strains showing unexpected genomic sequences. Nine genomic groups have been identified: the species Bovine viral diarrhea virus 1 (BVDV-1), Bovine viral diarrhea virus 2 (BVDV-2), Border disease virus (BDV) and Classical swine fever virus (CSFV) and the tentative species Pronghorn, Giraffe, Bovine viral diarrhea virus 3 (BVDV-3) (HoBi group), Border disease virus 2 (BDV-2) (Italian small ruminant isolates) and Bungowannah. Palindromic positions have been characterized according to changes in nucleotide base-pairs identifying low variable positions (LVP) including base-pairs present in less than 80% of the genus. The determination of divergence between single strain sequences or genetic groups was obtained easily by comparing base-pairing combinations from aligned secondary structures. This provided clear information such as the level of heterogeneity within a species, the relatedness between species, or facilitating the characterization and clustering of specific strains. The BVDV-1 and BDV species resulted heterogeneous, showing isolates located on a borderline in the species. Within the BVDV-2 species, two main genogroups were identified, with strains showing common sequence characteristics to both groups (multirelated strains). They could be allocated correctly by quantitative analysis. Similarly, the relation between CSFV and BDV species appeared very clearly. Also in this case, ambiguous strain sequences could be clustered in the
Manifold Regularized Reinforcement Learning.
Li, Hongliang; Liu, Derong; Wang, Ding
2018-04-01
This paper introduces a novel manifold regularized reinforcement learning scheme for continuous Markov decision processes. Smooth feature representations for value function approximation can be automatically learned using the unsupervised manifold regularization method. The learned features are data-driven, and can be adapted to the geometry of the state space. Furthermore, the scheme provides a direct basis representation extension for novel samples during policy learning and control. The performance of the proposed scheme is evaluated on two benchmark control tasks, i.e., the inverted pendulum and the energy storage problem. Simulation results illustrate the concepts of the proposed scheme and show that it can obtain excellent performance.
The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1.
Diccianni, M B; Imagawa, M; Muramatsu, M
1992-10-11
Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lack of a role for AP1 in GPEI mediated trans-activation in F9 cells, although endogenously present AP1 can influence GPEI in HeLa cells. Co-transfection of delta fosB with c-jun, which forms an inactive c-Jun/delta FosB heterodimer that binds TRE sequences, inhibits GPEI-mediated transcription in AP1-lacking F9 cells as well as AP1-containing HeLa cells. These data suggest novel factor(s) other than AP1 are influencing GPEI. Binding studies reveal multiple nucleoproteins bind to GPEI. These factors are likely responsible for the high level of GPEI-mediated transcription observed in the absence of AP1 and during hepatocarcinogenesis.
Czech Academy of Sciences Publication Activity Database
Charnavets, Tatsiana; Nunvář, Jaroslav; Nečasová, Iva; Voelker, J.; Breslauer, K.J.; Schneider, Bohdan
2015-01-01
Roč. 103, č. 10 (2015), s. 585-596 ISSN 0006-3525 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109; GA ČR GAP305/12/1801; GA MŠk(CZ) EE2.3.30.0020 Institutional support: RVO:86652036 Keywords : bacterial repetitive extragenic palindromes (REP) * circular dichroism spectroscopy * REP associated tyrosine transposases (RAYTs) Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.248, year: 2015
Female to male sex reversal was achieved in an emerging agricultural insect pest, Drosophila suzukii, by creating a temperature-sensitive point mutation in the sex-determination gene, transformer-2 (tra-2) using CRISPR/Cas9 (clustered regularly interspaced palindromic repeats/ CRISPR-associated) hom...
CRISPR-Cas9 Can Inhibit HIV-1 Replication but NHEJ Repair Facilitates Virus Escape
Wang, Gang; Zhao, Na; Berkhout, Ben; Das, Atze T.
2016-01-01
Several recent studies demonstrated that the clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease Cas9 can be used for guide RNA (gRNA)-directed, sequence-specific cleavage of HIV proviral DNA in infected cells. We here demonstrate profound inhibition of HIV-1
Discovery of "Escherichia coli" CRISPR Sequences in an Undergraduate Laboratory
Militello, Kevin T.; Lazatin, Justine C.
2017-01-01
Clustered regularly interspaced short palindromic repeats (CRISPRs) represent a novel type of adaptive immune system found in eubacteria and archaebacteria. CRISPRs have recently generated a lot of attention due to their unique ability to catalog foreign nucleic acids, their ability to destroy foreign nucleic acids in a mechanism that shares some…
In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration
Suzuki, Keiichiro; Tsunekawa, Yuji; Herná ndez-Bení tez, Reyna; Wu, Jun; Zhu, Jie; Kim, Euiseok J.; Hatanaka, Fumiyuki; Yamamoto, Mako; Araoka, Toshikazu; Li, Zhe; Kurita, Masakazu; Hishida, Tomoaki; Li, Mo; Aizawa, Emi; Guo, Shicheng; Chen, Song; Goebl, April; Soligalla, Rupa Devi; Qu, Jing; Jiang, Tingshuai; Fu, Xin; Jafari, Maryam; Esteban, Concepcion Rodriguez; Berggren, W. Travis; Lajara, Jeronimo; Nuñ ez-Delicado, Estrella; Guillen, Pedro; Campistol, Josep M.; Matsuzaki, Fumio; Liu, Guang-Hui; Magistretti, Pierre J.; Zhang, Kun; Callaway, Edward M.; Zhang, Kang; Belmonte, Juan Carlos Izpisua
2016-01-01
regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9)3, 4 technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more
A Golden Gate-based Protocol for Assembly of Multiplexed gRNA Expression Arrays for CRISPR/Cas9
DEFF Research Database (Denmark)
Vad-Nielsen, Johan; Lin, Lin; Jensen, Kristopher Torp
2016-01-01
The CRISPR (clustered regularly interspaced short palindromic repeats)-associated protein 9 (Cas9) has become the most broadly used and powerful tool for genome editing. Many applications of CRISPR-Cas9 require the delivery of multiple small guide RNAs (gRNAs) into the same cell in order to achieve...
Cas4 Facilitates PAM-Compatible Spacer Selection during CRISPR Adaptation
Kieper, S.N.; Almendros, Cristóbal; Behler, Juliane; McKenzie, R.E.; Luzia De Nóbrega, F.; van Eijkeren-Haagsma, A.C.; Vink, J.N.A.; Hess, Wolfgang R.; Brouns, S.J.J.
2018-01-01
CRISPR-Cas systems adapt their immunological memory against their invaders by integrating short DNA fragments into clustered regularly interspaced short palindromic repeat (CRISPR) loci. While Cas1 and Cas2 make up the core machinery of the CRISPR integration process, various class I and II
Seamless gene editing in Aspergillus species, using CRISPR-Cas9
DEFF Research Database (Denmark)
Nødvig, Christina Spuur; Hoof, Jakob Blæsbjerg; Mortensen, Uffe Hasbro
there are several obstacles slowing down the process. The harnessing of the prokaryotic and archaeal immune mechanism CRISPR (clustered regularly interspaced short palindromic repeats) as a tool for genetic engineering in eukaryotes, has proved to be a powerful technology. CRISPR/Cas9 introduces specific DNA double...
The Role of CRISPR-Cas Systems in Virulence of Pathogenic Bacteria
Louwen, R.; Staals, R.H.J.; Endtz, H.P.; Baarlen, van P.; Oost, van der J.
2014-01-01
Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) genes are present in many bacterial and archaeal genomes. Since the discovery of the typical CRISPR loci in the 1980s, well before their physiological role was revealed, their variable sequences have been
Application of CRISPR/Cas9 Genome Editing to Improve Recombinant Protein Production in CHO Cells
DEFF Research Database (Denmark)
Grav, Lise Marie; Julie la Cour Karottki, Karen; Lee, Jae Seong
2017-01-01
and yields. In this chapter, we present our protocol on how to use the genome editing tool Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) to knockout engineering target genes in CHO cells. As an example, we refer to the glutamine synthetase (GS...
Exploiting off-targeting in guide-RNAs for CRISPR systems for simultaneous editing of multiple genes
DEFF Research Database (Denmark)
Ferreira, Raphael; Gatto, Francesco; Nielsen, Jens
2017-01-01
Bioinformatics tools to design guide-RNAs (gRNAs) in Clustered Regularly Interspaced Short Palindromic Repeats systems mostly focused on minimizing off-targeting to enhance efficacy of genome editing. However, there are circumstances in which off-targeting might be desirable to target multiple ge...
Evolution and classification of the CRISPR-Cas systems
Makarova, K.S.; Brouns, S.J.J.; Oost, van der J.
2011-01-01
The CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) modules are adaptive immunity systems that are present in many archaea and bacteria. These defence systems are encoded by operons that have an extraordinarily diverse architecture and a high rate of
Cas4 Facilitates PAM-Compatible Spacer Selection during CRISPR Adaptation
Kieper, Sebastian N.; Almendros, Cristóbal; Behler, Juliane; McKenzie, Rebecca E.; Nobrega, Franklin L.; Haagsma, Anna C.; Vink, Jochem N.A.; Hess, Wolfgang R.; Brouns, Stan J.J.
2018-01-01
CRISPR-Cas systems adapt their immunological memory against their invaders by integrating short DNA fragments into clustered regularly interspaced short palindromic repeat (CRISPR) loci. While Cas1 and Cas2 make up the core machinery of the CRISPR integration process, various class I and II
CRISPR/Cas system for yeast genome engineering: advances and applications
DEFF Research Database (Denmark)
Stovicek, Vratislav; Holkenbrink, Carina; Borodina, Irina
2017-01-01
The methods based on the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated (Cas) system have quickly gained popularity for genome editing and transcriptional regulation in many organisms, including yeast. This review aims to provide a comprehensive overview...... of CRISPR application for different yeast species: from basic principles and genetic design to applications....
Crystal structure of the CRISPR RNA–guided surveillance complex from Escherichia coli
Jackson, R.N.; Golden, S.M.; Erp, P.B.; Carter, J.; Westra, E.R.; Brouns, S.J.J.; Oost, van der J.; Terwilliger, T.C.; Read, R.J.; Wiedenheft, B.
2014-01-01
Clustered regularly interspaced short palindromic repeats (CRISPRs) are essential components of RNA-guided adaptive immune systems that protect bacteria and archaea from viruses and plasmids. In Escherichia coli, short CRISPR-derived RNAs (crRNAs) assemble into a 405-kilodalton multisubunit
Antiviral Goes Viral : Harnessing CRISPR/Cas9 to Combat Viruses in Humans
Soppe, Jasper Adriaan; Lebbink, Robert Jan
2017-01-01
The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems are RNA-guided sequence-specific prokaryotic antiviral immune systems. In prokaryotes, small RNA molecules guide Cas effector endonucleases to invading foreign genetic elements in a
Small CRISPR RNAs guide antiviral defense in prokaryotes
Brouns, S.J.J.; Jore, M.M.; Lundgren, M.; Westra, E.R.; Slijkhuis, R.J.; Snijders, A.P.; Dickman, M.J.; Makarova, K.S.; Koonin, E.V.; Oost, van der J.
2008-01-01
Prokaryotes acquire virus resistance by integrating short fragments of viral nucleic acid into clusters of regularly interspaced short palindromic repeats (CRISPRs). Here we show how virus-derived sequences contained in CRISPRs are used by CRISPR-associated (Cas) proteins from the host to mediate an
Structural biology. Structures of the CRISPR-Cmr complex reveal mode of RNA target positioning
Taylor, D.W.; Zhu, Y.; Staals, R.H.J.; Kornfeld, J.E.; Shinkai, A.; Oost, van der J.; Nogales, E.; Doudna, J.A.
2015-01-01
Adaptive immunity in bacteria involves RNA-guided surveillance complexes that use CRISPR (clustered regularly interspaced short palindromic repeats)-associated (Cas) proteins together with CRISPR RNAs (crRNAs) to target invasive nucleic acids for degradation. Whereas type I and type II CRISPR-Cas
Degenerate target sites mediate rapid primed CRISPR adaptation
Fineran, P.C.; Gerritzen, M.J.; Suarez-Diez, M.; Kunne, T.; Boekhorst, J.; Hijum, S.A.F.T. van; Staals, R.H.G.; Brouns, S.J.
2014-01-01
Prokaryotes encode adaptive immune systems, called CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR associated), to provide resistance against mobile invaders, such as viruses and plasmids. Host immunity is based on incorporation of invader DNA sequences in a memory locus
Degenerate target sites mediate rapid primed CRISPR adaptation
Fineran, P.C.; Gerritzen, M.J.H.; Suarez Diez, M.; Künne, T.A.; Boekhorst, J.; Hijum, van S.A.F.T.; Staals, R.H.J.; Brouns, S.J.J.
2014-01-01
Prokaryotes encode adaptive immune systems, called CRISPR-Cas (clustered regularly interspaced short palindromic repeats–CRISPR associated), to provide resistance against mobile invaders, such as viruses and plasmids. Host immunity is based on incorporation of invader DNA sequences in a memory locus
The on–off switch of CRISPR immunity against phages in Escherichia coli
Mojica, Francisco J.M.; Díez-Villaseñor, César
2010-01-01
CRISPR/CAS is a novel prokaryotic defence system against cell invaders. A typical CRISPR/CAS system consists of one or more clusters of regularly interspaced short, often palindromic, repeats (CRISPR) followed at one side by an adenine- and thymine-rich (AT-rich) leader sequence, and a variable set of CAS (CRISPR associated) genes.
" Exploration into the roles of genes, the proteins that they encode, and the functions that they carry out within the cell is a founding pillar in the field of toxicology. Recent breakthroughs in clustered, regularly interspaced, short palindromic repeat (CRISPR) technology...
Johansen, Anne Katrine; Molenaar, Bas; Versteeg, Danielle; Leitoguinho, Ana Rita; Demkes, Charlotte; Spanjaard, Bastiaan; de Ruiter, Hesther; Akbari Moqadam, Farhad; Kooijman, Lieneke; Zentilin, Lorena; Giacca, Mauro; van Rooij, Eva
2017-01-01
RATIONALE: CRISPR/Cas9 (clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9)-based DNA editing has rapidly evolved as an attractive tool to modify the genome. Although CRISPR/Cas9 has been extensively used to manipulate the germline in zygotes, its application in
Oude Blenke, Erik; Evers, Martijn J.W.; Mastrobattista, Enrico; Oost, van der John
2016-01-01
The CRISPR-Cas9 gene editing system has taken the biomedical science field by storm, initiating rumors about future Nobel Prizes and heating up a fierce patent war, but also making significant scientific impact. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), together with
Diverse Regular Employees and Non-regular Employment (Japanese)
MORISHIMA Motohiro
2011-01-01
Currently there are high expectations for the introduction of policies related to diverse regular employees. These policies are a response to the problem of disparities between regular and non-regular employees (part-time, temporary, contract and other non-regular employees) and will make it more likely that workers can balance work and their private lives while companies benefit from the advantages of regular employment. In this paper, I look at two issues that underlie this discussion. The ...
Sparse structure regularized ranking
Wang, Jim Jing-Yan
2014-04-17
Learning ranking scores is critical for the multimedia database retrieval problem. In this paper, we propose a novel ranking score learning algorithm by exploring the sparse structure and using it to regularize ranking scores. To explore the sparse structure, we assume that each multimedia object could be represented as a sparse linear combination of all other objects, and combination coefficients are regarded as a similarity measure between objects and used to regularize their ranking scores. Moreover, we propose to learn the sparse combination coefficients and the ranking scores simultaneously. A unified objective function is constructed with regard to both the combination coefficients and the ranking scores, and is optimized by an iterative algorithm. Experiments on two multimedia database retrieval data sets demonstrate the significant improvements of the propose algorithm over state-of-the-art ranking score learning algorithms.
'Regular' and 'emergency' repair
International Nuclear Information System (INIS)
Luchnik, N.V.
1975-01-01
Experiments on the combined action of radiation and a DNA inhibitor using Crepis roots and on split-dose irradiation of human lymphocytes lead to the conclusion that there are two types of repair. The 'regular' repair takes place twice in each mitotic cycle and ensures the maintenance of genetic stability. The 'emergency' repair is induced at all stages of the mitotic cycle by high levels of injury. (author)
Regularization of divergent integrals
Felder, Giovanni; Kazhdan, David
2016-01-01
We study the Hadamard finite part of divergent integrals of differential forms with singularities on submanifolds. We give formulae for the dependence of the finite part on the choice of regularization and express them in terms of a suitable local residue map. The cases where the submanifold is a complex hypersurface in a complex manifold and where it is a boundary component of a manifold with boundary, arising in string perturbation theory, are treated in more detail.
Regularizing portfolio optimization
International Nuclear Information System (INIS)
Still, Susanne; Kondor, Imre
2010-01-01
The optimization of large portfolios displays an inherent instability due to estimation error. This poses a fundamental problem, because solutions that are not stable under sample fluctuations may look optimal for a given sample, but are, in effect, very far from optimal with respect to the average risk. In this paper, we approach the problem from the point of view of statistical learning theory. The occurrence of the instability is intimately related to over-fitting, which can be avoided using known regularization methods. We show how regularized portfolio optimization with the expected shortfall as a risk measure is related to support vector regression. The budget constraint dictates a modification. We present the resulting optimization problem and discuss the solution. The L2 norm of the weight vector is used as a regularizer, which corresponds to a diversification 'pressure'. This means that diversification, besides counteracting downward fluctuations in some assets by upward fluctuations in others, is also crucial because it improves the stability of the solution. The approach we provide here allows for the simultaneous treatment of optimization and diversification in one framework that enables the investor to trade off between the two, depending on the size of the available dataset.
Regularizing portfolio optimization
Still, Susanne; Kondor, Imre
2010-07-01
The optimization of large portfolios displays an inherent instability due to estimation error. This poses a fundamental problem, because solutions that are not stable under sample fluctuations may look optimal for a given sample, but are, in effect, very far from optimal with respect to the average risk. In this paper, we approach the problem from the point of view of statistical learning theory. The occurrence of the instability is intimately related to over-fitting, which can be avoided using known regularization methods. We show how regularized portfolio optimization with the expected shortfall as a risk measure is related to support vector regression. The budget constraint dictates a modification. We present the resulting optimization problem and discuss the solution. The L2 norm of the weight vector is used as a regularizer, which corresponds to a diversification 'pressure'. This means that diversification, besides counteracting downward fluctuations in some assets by upward fluctuations in others, is also crucial because it improves the stability of the solution. The approach we provide here allows for the simultaneous treatment of optimization and diversification in one framework that enables the investor to trade off between the two, depending on the size of the available dataset.
Regular Single Valued Neutrosophic Hypergraphs
Directory of Open Access Journals (Sweden)
Muhammad Aslam Malik
2016-12-01
Full Text Available In this paper, we define the regular and totally regular single valued neutrosophic hypergraphs, and discuss the order and size along with properties of regular and totally regular single valued neutrosophic hypergraphs. We also extend work on completeness of single valued neutrosophic hypergraphs.
The geometry of continuum regularization
International Nuclear Information System (INIS)
Halpern, M.B.
1987-03-01
This lecture is primarily an introduction to coordinate-invariant regularization, a recent advance in the continuum regularization program. In this context, the program is seen as fundamentally geometric, with all regularization contained in regularized DeWitt superstructures on field deformations
Sola, Christophe
2015-06-01
The natural history of tuberculosis may be tackled by various means, among which the record of molecular scars that have been registered by the Mycobacterium tuberculosis complex (MTBC) genomes transmitted from patient to patient for tens of thousands years and possibly more. Recently discovered polymorphic loci, the CRISPR sequences, are indirect witnesses of the historical phage-bacteria struggle, and may be related to the time when the ancestor of today's tubercle bacilli were environmental bacteria, i.e. before becoming intracellular parasites. In this article, we present what are CRISPRs and try to summarize almost 20 years of research results obtained using the genetic diversity of the CRISPR loci in MTBC as a perspective for studying new models. We show that the study of the diversity of CRISPR sequences, thanks to «spoligotyping», has played a great role in our global understanding of the population structure of MTBC. Copyright © 2015 Elsevier Ltd. All rights reserved.
Annotation of Regular Polysemy
DEFF Research Database (Denmark)
Martinez Alonso, Hector
Regular polysemy has received a lot of attention from the theory of lexical semantics and from computational linguistics. However, there is no consensus on how to represent the sense of underspecified examples at the token level, namely when annotating or disambiguating senses of metonymic words...... and metonymic. We have conducted an analysis in English, Danish and Spanish. Later on, we have tried to replicate the human judgments by means of unsupervised and semi-supervised sense prediction. The automatic sense-prediction systems have been unable to find empiric evidence for the underspecified sense, even...
Regularity of Minimal Surfaces
Dierkes, Ulrich; Tromba, Anthony J; Kuster, Albrecht
2010-01-01
"Regularity of Minimal Surfaces" begins with a survey of minimal surfaces with free boundaries. Following this, the basic results concerning the boundary behaviour of minimal surfaces and H-surfaces with fixed or free boundaries are studied. In particular, the asymptotic expansions at interior and boundary branch points are derived, leading to general Gauss-Bonnet formulas. Furthermore, gradient estimates and asymptotic expansions for minimal surfaces with only piecewise smooth boundaries are obtained. One of the main features of free boundary value problems for minimal surfaces is t
Regularities of radiation heredity
International Nuclear Information System (INIS)
Skakov, M.K.; Melikhov, V.D.
2001-01-01
One analyzed regularities of radiation heredity in metals and alloys. One made conclusion about thermodynamically irreversible changes in structure of materials under irradiation. One offers possible ways of heredity transmittance of radiation effects at high-temperature transformations in the materials. Phenomenon of radiation heredity may be turned to practical use to control structure of liquid metal and, respectively, structure of ingot via preliminary radiation treatment of charge. Concentration microheterogeneities in material defect structure induced by preliminary irradiation represent the genetic factor of radiation heredity [ru
Directory of Open Access Journals (Sweden)
Glass John I
2010-07-01
repeat may be disseminated by HGT and intra-genomic shuffling. Conclusions We describe novel features of PARCELs (Palindromic Amphipathic Repeat Coding ELements, a set of widely distributed repeat protein domains and coding sequences that were likely acquired through HGT by diverse unicellular microbes, further mobilized and diversified within genomes, and co-opted for expression in the membrane proteome of some taxa. Disseminated by multiple gene-centric vehicles, ORFs harboring these elements enhance accessory gene pools as part of the "mobilome" connecting genomes of various clades, in taxa sharing common niches.
Rizvi, Tahir A; Kenyon, Julia C; Ali, Jahabar; Aktar, Suriya J; Phillip, Pretty S; Ghazawi, Akela; Mustafa, Farah; Lever, Andrew M L
2010-10-15
The feline immunodeficiency virus (FIV) is a lentivirus that is related to human immunodeficiency virus (HIV), causing a similar pathology in cats. It is a potential small animal model for AIDS and the FIV-based vectors are also being pursued for human gene therapy. Previous studies have mapped the FIV packaging signal (ψ) to two or more discontinuous regions within the 5' 511 nt of the genomic RNA and structural analyses have determined its secondary structure. The 5' and 3' sequences within ψ region interact through extensive long-range interactions (LRIs), including a conserved heptanucleotide interaction between R/U5 and gag. Other secondary structural elements identified include a conserved 150 nt stem-loop (SL2) and a small palindromic stem-loop within gag open reading frame that might act as a viral dimerization initiation site. We have performed extensive mutational analysis of these sequences and structures and ascertained their importance in FIV packaging using a trans-complementation assay. Disrupting the conserved heptanucleotide LRI to prevent base pairing between R/U5 and gag reduced packaging by 2.8-5.5 fold. Restoration of pairing using an alternative, non-wild type (wt) LRI sequence restored RNA packaging and propagation to wt levels, suggesting that it is the structure of the LRI, rather than its sequence, that is important for FIV packaging. Disrupting the palindrome within gag reduced packaging by 1.5-3-fold, but substitution with a different palindromic sequence did not restore packaging completely, suggesting that the sequence of this region as well as its palindromic nature is important. Mutation of individual regions of SL2 did not have a pronounced effect on FIV packaging, suggesting that either it is the structure of SL2 as a whole that is necessary for optimal packaging, or that there is redundancy within this structure. The mutational analysis presented here has further validated the previously predicted RNA secondary structure of FIV
Effective field theory dimensional regularization
International Nuclear Information System (INIS)
Lehmann, Dirk; Prezeau, Gary
2002-01-01
A Lorentz-covariant regularization scheme for effective field theories with an arbitrary number of propagating heavy and light particles is given. This regularization scheme leaves the low-energy analytic structure of Greens functions intact and preserves all the symmetries of the underlying Lagrangian. The power divergences of regularized loop integrals are controlled by the low-energy kinematic variables. Simple diagrammatic rules are derived for the regularization of arbitrary one-loop graphs and the generalization to higher loops is discussed
Effective field theory dimensional regularization
Lehmann, Dirk; Prézeau, Gary
2002-01-01
A Lorentz-covariant regularization scheme for effective field theories with an arbitrary number of propagating heavy and light particles is given. This regularization scheme leaves the low-energy analytic structure of Greens functions intact and preserves all the symmetries of the underlying Lagrangian. The power divergences of regularized loop integrals are controlled by the low-energy kinematic variables. Simple diagrammatic rules are derived for the regularization of arbitrary one-loop graphs and the generalization to higher loops is discussed.
2010-12-07
... FARM CREDIT SYSTEM INSURANCE CORPORATION Regular Meeting AGENCY: Farm Credit System Insurance Corporation Board. ACTION: Regular meeting. SUMMARY: Notice is hereby given of the regular meeting of the Farm Credit System Insurance Corporation Board (Board). Date and Time: The meeting of the Board will be held...
Selection of regularization parameter for l1-regularized damage detection
Hou, Rongrong; Xia, Yong; Bao, Yuequan; Zhou, Xiaoqing
2018-06-01
The l1 regularization technique has been developed for structural health monitoring and damage detection through employing the sparsity condition of structural damage. The regularization parameter, which controls the trade-off between data fidelity and solution size of the regularization problem, exerts a crucial effect on the solution. However, the l1 regularization problem has no closed-form solution, and the regularization parameter is usually selected by experience. This study proposes two strategies of selecting the regularization parameter for the l1-regularized damage detection problem. The first method utilizes the residual and solution norms of the optimization problem and ensures that they are both small. The other method is based on the discrepancy principle, which requires that the variance of the discrepancy between the calculated and measured responses is close to the variance of the measurement noise. The two methods are applied to a cantilever beam and a three-story frame. A range of the regularization parameter, rather than one single value, can be determined. When the regularization parameter in this range is selected, the damage can be accurately identified even for multiple damage scenarios. This range also indicates the sensitivity degree of the damage identification problem to the regularization parameter.
Ensemble manifold regularization.
Geng, Bo; Tao, Dacheng; Xu, Chao; Yang, Linjun; Hua, Xian-Sheng
2012-06-01
We propose an automatic approximation of the intrinsic manifold for general semi-supervised learning (SSL) problems. Unfortunately, it is not trivial to define an optimization function to obtain optimal hyperparameters. Usually, cross validation is applied, but it does not necessarily scale up. Other problems derive from the suboptimality incurred by discrete grid search and the overfitting. Therefore, we develop an ensemble manifold regularization (EMR) framework to approximate the intrinsic manifold by combining several initial guesses. Algorithmically, we designed EMR carefully so it 1) learns both the composite manifold and the semi-supervised learner jointly, 2) is fully automatic for learning the intrinsic manifold hyperparameters implicitly, 3) is conditionally optimal for intrinsic manifold approximation under a mild and reasonable assumption, and 4) is scalable for a large number of candidate manifold hyperparameters, from both time and space perspectives. Furthermore, we prove the convergence property of EMR to the deterministic matrix at rate root-n. Extensive experiments over both synthetic and real data sets demonstrate the effectiveness of the proposed framework.
Adaptive Regularization of Neural Classifiers
DEFF Research Database (Denmark)
Andersen, Lars Nonboe; Larsen, Jan; Hansen, Lars Kai
1997-01-01
We present a regularization scheme which iteratively adapts the regularization parameters by minimizing the validation error. It is suggested to use the adaptive regularization scheme in conjunction with optimal brain damage pruning to optimize the architecture and to avoid overfitting. Furthermo......, we propose an improved neural classification architecture eliminating an inherent redundancy in the widely used SoftMax classification network. Numerical results demonstrate the viability of the method...
Stankovic, Uros; van Herk, Marcel; Ploeger, Lennert S; Sonke, Jan-Jakob
2014-06-01
Medical linear accelerator mounted cone beam CT (CBCT) scanner provides useful soft tissue contrast for purposes of image guidance in radiotherapy. The presence of extensive scattered radiation has a negative effect on soft tissue visibility and uniformity of CBCT scans. Antiscatter grids (ASG) are used in the field of diagnostic radiography to mitigate the scatter. They usually do increase the contrast of the scan, but simultaneously increase the noise. Therefore, and considering other scatter mitigation mechanisms present in a CBCT scanner, the applicability of ASGs with aluminum interspacing for a wide range of imaging conditions has been inconclusive in previous studies. In recent years, grids using fiber interspacers have appeared, providing grids with higher scatter rejection while maintaining reasonable transmission of primary radiation. The purpose of this study was to evaluate the impact of one such grid on CBCT image quality. The grid used (Philips Medical Systems) had ratio of 21:1, frequency 36 lp/cm, and nominal selectivity of 11.9. It was mounted on the kV flat panel detector of an Elekta Synergy linear accelerator and tested in a phantom and a clinical study. Due to the flex of the linac and presence of gridline artifacts an angle dependent gain correction algorithm was devised to mitigate resulting artifacts. Scan reconstruction was performed using XVI4.5 augmented with inhouse developed image lag correction and Hounsfield unit calibration. To determine the necessary parameters for Hounsfield unit calibration and software scatter correction parameters, the Catphan 600 (The Phantom Laboratory) phantom was used. Image quality parameters were evaluated using CIRS CBCT Image Quality and Electron Density Phantom (CIRS) in two different geometries: one modeling head and neck and other pelvic region. Phantoms were acquired with and without the grid and reconstructed with and without software correction which was adapted for the different acquisition
International Nuclear Information System (INIS)
Stankovic, Uros; Herk, Marcel van; Ploeger, Lennert S.; Sonke, Jan-Jakob
2014-01-01
Purpose: Medical linear accelerator mounted cone beam CT (CBCT) scanner provides useful soft tissue contrast for purposes of image guidance in radiotherapy. The presence of extensive scattered radiation has a negative effect on soft tissue visibility and uniformity of CBCT scans. Antiscatter grids (ASG) are used in the field of diagnostic radiography to mitigate the scatter. They usually do increase the contrast of the scan, but simultaneously increase the noise. Therefore, and considering other scatter mitigation mechanisms present in a CBCT scanner, the applicability of ASGs with aluminum interspacing for a wide range of imaging conditions has been inconclusive in previous studies. In recent years, grids using fiber interspacers have appeared, providing grids with higher scatter rejection while maintaining reasonable transmission of primary radiation. The purpose of this study was to evaluate the impact of one such grid on CBCT image quality. Methods: The grid used (Philips Medical Systems) had ratio of 21:1, frequency 36 lp/cm, and nominal selectivity of 11.9. It was mounted on the kV flat panel detector of an Elekta Synergy linear accelerator and tested in a phantom and a clinical study. Due to the flex of the linac and presence of gridline artifacts an angle dependent gain correction algorithm was devised to mitigate resulting artifacts. Scan reconstruction was performed using XVI4.5 augmented with inhouse developed image lag correction and Hounsfield unit calibration. To determine the necessary parameters for Hounsfield unit calibration and software scatter correction parameters, the Catphan 600 (The Phantom Laboratory) phantom was used. Image quality parameters were evaluated using CIRS CBCT Image Quality and Electron Density Phantom (CIRS) in two different geometries: one modeling head and neck and other pelvic region. Phantoms were acquired with and without the grid and reconstructed with and without software correction which was adapted for the different
Giangaspero, Massimo; Apicella, Claudio; Harasawa, Ryô
2013-09-01
The genus Pestivirus from the family Flaviviridae is represented by four established species; Bovine viral diarrhea virus 1 (BVDV-1); Bovine viral diarrhea virus 2 (BVDV-2); Border disease virus (BDV); and Classical swine fever virus (CSFV); as well a tentative species from a Giraffe. The palindromic nucleotide substitutions (PNS) in the 5' untranslated region (UTR) of Pestivirus RNA has been described as a new, simple and practical method for genotyping. New software is described, also named PNS, that was prepared specifically for this PNS genotyping procedure. Pestivirus identification using PNS was evaluated on five hundred and forty-three sequences at genus, species and genotype level using this software. The software is freely available at www.pns-software.com. Copyright © 2013 Elsevier B.V. All rights reserved.
Crystal Structure of the Dimeric Oct6 (Pou3fl) POU Domain Bound to Palindromic MORE DNA
Energy Technology Data Exchange (ETDEWEB)
R Jauch; S Choo; C Ng; P Kolatkar
2011-12-31
POU domains (named after their identification in Pit1, Oct1 unc86) are found in around 15 transcription factors encoded in mammalian genomes many of which feature prominently as key regulators at development bifurcations. For example, the POU III class Octamer binding protein 6 (Oct6) is expressed in embryonic stem cells and during neural development and drives the differentia5tion of myelinated cells in the central and peripheral nervous system. Defects in oct6 expression levels are linked to neurological disorders such as schizophrenia. POU proteins contain a bi-partite DNA binding domain that assembles on various DNA motifs with differentially configured subdomains. Intriguingly, alternative configurations of POU domains on different DNA sites were shown to affect the subsequent recruitment of transcriptional coactivators. Namely, binding of Oct1 to a Palindromic Oct-factor Recognition Element (PORE) was shown to facilitate the recruitment of the OBF1 coactivator whereas More of PORE (MORE) bound Oct1 does not. Moreover, Pit1 was shown to recruit the corepressor N-CoR only when bound to a variant MORE motif with a 2 bp half-site spacing. Therefore, POU proteins are seen as a paradigm for DNA induced allosteric effects on transcription factors modulating their regulatory potential. However, a big unresolved conundrum for the POU class and for most if not all other transcription factor classes is how highly similar proteins regulate different sets of genes causing fundamentally different biological responses. Ultimately, there must be subtle features enabling those factors to engage in contrasting molecular interactions in the cell. Thus, the dissection of the molecular details of the transcription-DNA recognition in general, and the formation of multimeric regulatory complexes, in particular, is highly desirable. To contribute to these efforts they solved the 2.05 {angstrom} crystal structure of Oct6 bound as a symmetrical homodimer to palindromic MORE DNA.
2010-09-02
... FARM CREDIT SYSTEM INSURANCE CORPORATION Regular Meeting AGENCY: Farm Credit System Insurance Corporation Board. SUMMARY: Notice is hereby given of the regular meeting of the Farm Credit System Insurance Corporation Board (Board). DATE AND TIME: The meeting of the Board will be held at the offices of the Farm...
Online co-regularized algorithms
Ruijter, T. de; Tsivtsivadze, E.; Heskes, T.
2012-01-01
We propose an online co-regularized learning algorithm for classification and regression tasks. We demonstrate that by sequentially co-regularizing prediction functions on unlabeled data points, our algorithm provides improved performance in comparison to supervised methods on several UCI benchmarks
García, Raquel; García, Mauricio; Ogando, Francisco; Pampin, Raúl; Sanz, Javier
2017-09-01
This paper explores the quality of available activation cross section (XS) data for accurate Shutdown Dose Rate (SDDR) prediction in the ITER Port Cell and Port Interspace areas, where different maintenance activities are foreseen. For this purpose the EAF library (2007 and 2010 versions) has been investigated, as it is typically used by the ITER community. Based on both reports/papers on SDDR in ITER and own calculations, major nuclides contributing to the SDDR coming from the activation of i) relevant materials placed in ITER and ii) candidate materials for the bioshield plug as L2N and barite concretes, are identified. Then, relevant production pathways are obtained. EAF XS quality for all pathways is checked following the procedure used for validating and testing the successive EAF versions. Also, possible improvements from using the TENDL-2015 library are assessed by comparing EAF and TENDL XS with available differential experimental data from EXFOR. Results point out that most of the activation XS related to materials currently placed in ITER are reliable, and only a few need improvement. Also, many of the XS related to both L2N and barite concretes need further work for validation.
Continuum-regularized quantum gravity
International Nuclear Information System (INIS)
Chan Huesum; Halpern, M.B.
1987-01-01
The recent continuum regularization of d-dimensional Euclidean gravity is generalized to arbitrary power-law measure and studied in some detail as a representative example of coordinate-invariant regularization. The weak-coupling expansion of the theory illustrates a generic geometrization of regularized Schwinger-Dyson rules, generalizing previous rules in flat space and flat superspace. The rules are applied in a non-trivial explicit check of Einstein invariance at one loop: the cosmological counterterm is computed and its contribution is included in a verification that the graviton mass is zero. (orig.)
New regular black hole solutions
International Nuclear Information System (INIS)
Lemos, Jose P. S.; Zanchin, Vilson T.
2011-01-01
In the present work we consider general relativity coupled to Maxwell's electromagnetism and charged matter. Under the assumption of spherical symmetry, there is a particular class of solutions that correspond to regular charged black holes whose interior region is de Sitter, the exterior region is Reissner-Nordstroem and there is a charged thin-layer in-between the two. The main physical and geometrical properties of such charged regular black holes are analyzed.
Regular variation on measure chains
Czech Academy of Sciences Publication Activity Database
Řehák, Pavel; Vitovec, J.
2010-01-01
Roč. 72, č. 1 (2010), s. 439-448 ISSN 0362-546X R&D Projects: GA AV ČR KJB100190701 Institutional research plan: CEZ:AV0Z10190503 Keywords : regularly varying function * regularly varying sequence * measure chain * time scale * embedding theorem * representation theorem * second order dynamic equation * asymptotic properties Subject RIV: BA - General Mathematics Impact factor: 1.279, year: 2010 http://www.sciencedirect.com/science/article/pii/S0362546X09008475
Manifold Regularized Correlation Object Tracking
Hu, Hongwei; Ma, Bo; Shen, Jianbing; Shao, Ling
2017-01-01
In this paper, we propose a manifold regularized correlation tracking method with augmented samples. To make better use of the unlabeled data and the manifold structure of the sample space, a manifold regularization-based correlation filter is introduced, which aims to assign similar labels to neighbor samples. Meanwhile, the regression model is learned by exploiting the block-circulant structure of matrices resulting from the augmented translated samples over multiple base samples cropped fr...
On geodesics in low regularity
Sämann, Clemens; Steinbauer, Roland
2018-02-01
We consider geodesics in both Riemannian and Lorentzian manifolds with metrics of low regularity. We discuss existence of extremal curves for continuous metrics and present several old and new examples that highlight their subtle interrelation with solutions of the geodesic equations. Then we turn to the initial value problem for geodesics for locally Lipschitz continuous metrics and generalize recent results on existence, regularity and uniqueness of solutions in the sense of Filippov.
Condition Number Regularized Covariance Estimation.
Won, Joong-Ho; Lim, Johan; Kim, Seung-Jean; Rajaratnam, Bala
2013-06-01
Estimation of high-dimensional covariance matrices is known to be a difficult problem, has many applications, and is of current interest to the larger statistics community. In many applications including so-called the "large p small n " setting, the estimate of the covariance matrix is required to be not only invertible, but also well-conditioned. Although many regularization schemes attempt to do this, none of them address the ill-conditioning problem directly. In this paper, we propose a maximum likelihood approach, with the direct goal of obtaining a well-conditioned estimator. No sparsity assumption on either the covariance matrix or its inverse are are imposed, thus making our procedure more widely applicable. We demonstrate that the proposed regularization scheme is computationally efficient, yields a type of Steinian shrinkage estimator, and has a natural Bayesian interpretation. We investigate the theoretical properties of the regularized covariance estimator comprehensively, including its regularization path, and proceed to develop an approach that adaptively determines the level of regularization that is required. Finally, we demonstrate the performance of the regularized estimator in decision-theoretic comparisons and in the financial portfolio optimization setting. The proposed approach has desirable properties, and can serve as a competitive procedure, especially when the sample size is small and when a well-conditioned estimator is required.
Condition Number Regularized Covariance Estimation*
Won, Joong-Ho; Lim, Johan; Kim, Seung-Jean; Rajaratnam, Bala
2012-01-01
Estimation of high-dimensional covariance matrices is known to be a difficult problem, has many applications, and is of current interest to the larger statistics community. In many applications including so-called the “large p small n” setting, the estimate of the covariance matrix is required to be not only invertible, but also well-conditioned. Although many regularization schemes attempt to do this, none of them address the ill-conditioning problem directly. In this paper, we propose a maximum likelihood approach, with the direct goal of obtaining a well-conditioned estimator. No sparsity assumption on either the covariance matrix or its inverse are are imposed, thus making our procedure more widely applicable. We demonstrate that the proposed regularization scheme is computationally efficient, yields a type of Steinian shrinkage estimator, and has a natural Bayesian interpretation. We investigate the theoretical properties of the regularized covariance estimator comprehensively, including its regularization path, and proceed to develop an approach that adaptively determines the level of regularization that is required. Finally, we demonstrate the performance of the regularized estimator in decision-theoretic comparisons and in the financial portfolio optimization setting. The proposed approach has desirable properties, and can serve as a competitive procedure, especially when the sample size is small and when a well-conditioned estimator is required. PMID:23730197
Geometric continuum regularization of quantum field theory
International Nuclear Information System (INIS)
Halpern, M.B.
1989-01-01
An overview of the continuum regularization program is given. The program is traced from its roots in stochastic quantization, with emphasis on the examples of regularized gauge theory, the regularized general nonlinear sigma model and regularized quantum gravity. In its coordinate-invariant form, the regularization is seen as entirely geometric: only the supermetric on field deformations is regularized, and the prescription provides universal nonperturbative invariant continuum regularization across all quantum field theory. 54 refs
Metric regularity and subdifferential calculus
International Nuclear Information System (INIS)
Ioffe, A D
2000-01-01
The theory of metric regularity is an extension of two classical results: the Lyusternik tangent space theorem and the Graves surjection theorem. Developments in non-smooth analysis in the 1980s and 1990s paved the way for a number of far-reaching extensions of these results. It was also well understood that the phenomena behind the results are of metric origin, not connected with any linear structure. At the same time it became clear that some basic hypotheses of the subdifferential calculus are closely connected with the metric regularity of certain set-valued maps. The survey is devoted to the metric theory of metric regularity and its connection with subdifferential calculus in Banach spaces
Manifold Regularized Correlation Object Tracking.
Hu, Hongwei; Ma, Bo; Shen, Jianbing; Shao, Ling
2018-05-01
In this paper, we propose a manifold regularized correlation tracking method with augmented samples. To make better use of the unlabeled data and the manifold structure of the sample space, a manifold regularization-based correlation filter is introduced, which aims to assign similar labels to neighbor samples. Meanwhile, the regression model is learned by exploiting the block-circulant structure of matrices resulting from the augmented translated samples over multiple base samples cropped from both target and nontarget regions. Thus, the final classifier in our method is trained with positive, negative, and unlabeled base samples, which is a semisupervised learning framework. A block optimization strategy is further introduced to learn a manifold regularization-based correlation filter for efficient online tracking. Experiments on two public tracking data sets demonstrate the superior performance of our tracker compared with the state-of-the-art tracking approaches.
Dimensional regularization in configuration space
International Nuclear Information System (INIS)
Bollini, C.G.; Giambiagi, J.J.
1995-09-01
Dimensional regularization is introduced in configuration space by Fourier transforming in D-dimensions the perturbative momentum space Green functions. For this transformation, Bochner theorem is used, no extra parameters, such as those of Feynman or Bogoliubov-Shirkov are needed for convolutions. The regularized causal functions in x-space have ν-dependent moderated singularities at the origin. They can be multiplied together and Fourier transformed (Bochner) without divergence problems. The usual ultraviolet divergences appear as poles of the resultant functions of ν. Several example are discussed. (author). 9 refs
Regular algebra and finite machines
Conway, John Horton
2012-01-01
World-famous mathematician John H. Conway based this classic text on a 1966 course he taught at Cambridge University. Geared toward graduate students of mathematics, it will also prove a valuable guide to researchers and professional mathematicians.His topics cover Moore's theory of experiments, Kleene's theory of regular events and expressions, Kleene algebras, the differential calculus of events, factors and the factor matrix, and the theory of operators. Additional subjects include event classes and operator classes, some regulator algebras, context-free languages, communicative regular alg
Matrix regularization of 4-manifolds
Trzetrzelewski, M.
2012-01-01
We consider products of two 2-manifolds such as S^2 x S^2, embedded in Euclidean space and show that the corresponding 4-volume preserving diffeomorphism algebra can be approximated by a tensor product SU(N)xSU(N) i.e. functions on a manifold are approximated by the Kronecker product of two SU(N) matrices. A regularization of the 4-sphere is also performed by constructing N^2 x N^2 matrix representations of the 4-algebra (and as a byproduct of the 3-algebra which makes the regularization of S...
Regularization of Nonmonotone Variational Inequalities
International Nuclear Information System (INIS)
Konnov, Igor V.; Ali, M.S.S.; Mazurkevich, E.O.
2006-01-01
In this paper we extend the Tikhonov-Browder regularization scheme from monotone to rather a general class of nonmonotone multivalued variational inequalities. We show that their convergence conditions hold for some classes of perfectly and nonperfectly competitive economic equilibrium problems
Lattice regularized chiral perturbation theory
International Nuclear Information System (INIS)
Borasoy, Bugra; Lewis, Randy; Ouimet, Pierre-Philippe A.
2004-01-01
Chiral perturbation theory can be defined and regularized on a spacetime lattice. A few motivations are discussed here, and an explicit lattice Lagrangian is reviewed. A particular aspect of the connection between lattice chiral perturbation theory and lattice QCD is explored through a study of the Wess-Zumino-Witten term
2011-01-20
... Meeting SUMMARY: Notice is hereby given of the regular meeting of the Farm Credit System Insurance Corporation Board (Board). Date and Time: The meeting of the Board will be held at the offices of the Farm... meeting of the Board will be open to the [[Page 3630
Forcing absoluteness and regularity properties
Ikegami, D.
2010-01-01
For a large natural class of forcing notions, we prove general equivalence theorems between forcing absoluteness statements, regularity properties, and transcendence properties over L and the core model K. We use our results to answer open questions from set theory of the reals.
Globals of Completely Regular Monoids
Institute of Scientific and Technical Information of China (English)
Wu Qian-qian; Gan Ai-ping; Du Xian-kun
2015-01-01
An element of a semigroup S is called irreducible if it cannot be expressed as a product of two elements in S both distinct from itself. In this paper we show that the class C of all completely regular monoids with irreducible identity elements satisfies the strong isomorphism property and so it is globally determined.
Fluid queues and regular variation
Boxma, O.J.
1996-01-01
This paper considers a fluid queueing system, fed by N independent sources that alternate between silence and activity periods. We assume that the distribution of the activity periods of one or more sources is a regularly varying function of index ¿. We show that its fat tail gives rise to an even
Fluid queues and regular variation
O.J. Boxma (Onno)
1996-01-01
textabstractThis paper considers a fluid queueing system, fed by $N$ independent sources that alternate between silence and activity periods. We assume that the distribution of the activity periods of one or more sources is a regularly varying function of index $zeta$. We show that its fat tail
Empirical laws, regularity and necessity
Koningsveld, H.
1973-01-01
In this book I have tried to develop an analysis of the concept of an empirical law, an analysis that differs in many ways from the alternative analyse's found in contemporary literature dealing with the subject.
1 am referring especially to two well-known views, viz. the regularity and
Interval matrices: Regularity generates singularity
Czech Academy of Sciences Publication Activity Database
Rohn, Jiří; Shary, S.P.
2018-01-01
Roč. 540, 1 March (2018), s. 149-159 ISSN 0024-3795 Institutional support: RVO:67985807 Keywords : interval matrix * regularity * singularity * P-matrix * absolute value equation * diagonally singilarizable matrix Subject RIV: BA - General Mathematics Impact factor: 0.973, year: 2016
Regularization in Matrix Relevance Learning
Schneider, Petra; Bunte, Kerstin; Stiekema, Han; Hammer, Barbara; Villmann, Thomas; Biehl, Michael
A In this paper, we present a regularization technique to extend recently proposed matrix learning schemes in learning vector quantization (LVQ). These learning algorithms extend the concept of adaptive distance measures in LVQ to the use of relevance matrices. In general, metric learning can
Directory of Open Access Journals (Sweden)
J. Gong
2018-01-01
Full Text Available We used process-based modelling to investigate the roles of carbon-flux (C-flux components and plant–interspace heterogeneities in regulating soil CO2 exchanges (FS in a dryland ecosystem with sparse vegetation. To simulate the diurnal and seasonal dynamics of FS, the modelling considered simultaneously the CO2 production, transport and surface exchanges (e.g. biocrust photosynthesis, respiration and photodegradation. The model was parameterized and validated with multivariate data measured during the years 2013–2014 in a semiarid shrubland ecosystem in Yanchi, northwestern China. The model simulation showed that soil rewetting could enhance CO2 dissolution and delay the emission of CO2 produced from rooting zone. In addition, an ineligible fraction of respired CO2 might be removed from soil volumes under respiration chambers by lateral water flows and root uptakes. During rewetting, the lichen-crusted soil could shift temporally from net CO2 source to sink due to the activated photosynthesis of biocrust but the restricted CO2 emissions from subsoil. The presence of plant cover could decrease the root-zone CO2 production and biocrust C sequestration but increase the temperature sensitivities of these fluxes. On the other hand, the sensitivities of root-zone emissions to water content were lower under canopy, which may be due to the advection of water flows from the interspace to canopy. To conclude, the complexity and plant–interspace heterogeneities of soil C processes should be carefully considered to extrapolate findings from chamber to ecosystem scales and to predict the ecosystem responses to climate change and extreme climatic events. Our model can serve as a useful tool to simulate the soil CO2 efflux dynamics in dryland ecosystems.
Gong, Jinnan; Wang, Ben; Jia, Xin; Feng, Wei; Zha, Tianshan; Kellomäki, Seppo; Peltola, Heli
2018-01-01
We used process-based modelling to investigate the roles of carbon-flux (C-flux) components and plant-interspace heterogeneities in regulating soil CO2 exchanges (FS) in a dryland ecosystem with sparse vegetation. To simulate the diurnal and seasonal dynamics of FS, the modelling considered simultaneously the CO2 production, transport and surface exchanges (e.g. biocrust photosynthesis, respiration and photodegradation). The model was parameterized and validated with multivariate data measured during the years 2013-2014 in a semiarid shrubland ecosystem in Yanchi, northwestern China. The model simulation showed that soil rewetting could enhance CO2 dissolution and delay the emission of CO2 produced from rooting zone. In addition, an ineligible fraction of respired CO2 might be removed from soil volumes under respiration chambers by lateral water flows and root uptakes. During rewetting, the lichen-crusted soil could shift temporally from net CO2 source to sink due to the activated photosynthesis of biocrust but the restricted CO2 emissions from subsoil. The presence of plant cover could decrease the root-zone CO2 production and biocrust C sequestration but increase the temperature sensitivities of these fluxes. On the other hand, the sensitivities of root-zone emissions to water content were lower under canopy, which may be due to the advection of water flows from the interspace to canopy. To conclude, the complexity and plant-interspace heterogeneities of soil C processes should be carefully considered to extrapolate findings from chamber to ecosystem scales and to predict the ecosystem responses to climate change and extreme climatic events. Our model can serve as a useful tool to simulate the soil CO2 efflux dynamics in dryland ecosystems.
Regular and conformal regular cores for static and rotating solutions
Energy Technology Data Exchange (ETDEWEB)
Azreg-Aïnou, Mustapha
2014-03-07
Using a new metric for generating rotating solutions, we derive in a general fashion the solution of an imperfect fluid and that of its conformal homolog. We discuss the conditions that the stress–energy tensors and invariant scalars be regular. On classical physical grounds, it is stressed that conformal fluids used as cores for static or rotating solutions are exempt from any malicious behavior in that they are finite and defined everywhere.
Regular and conformal regular cores for static and rotating solutions
International Nuclear Information System (INIS)
Azreg-Aïnou, Mustapha
2014-01-01
Using a new metric for generating rotating solutions, we derive in a general fashion the solution of an imperfect fluid and that of its conformal homolog. We discuss the conditions that the stress–energy tensors and invariant scalars be regular. On classical physical grounds, it is stressed that conformal fluids used as cores for static or rotating solutions are exempt from any malicious behavior in that they are finite and defined everywhere.
Huang, Tsung-Ming; Lin, Wen-Wei; Tian, Heng; Chen, Guan-Hua
2018-03-01
Full spectrum of a large sparse ⊤-palindromic quadratic eigenvalue problem (⊤-PQEP) is considered arguably for the first time in this article. Such a problem is posed by calculation of surface Green's functions (SGFs) of mesoscopic transistors with a tremendous non-periodic cross-section. For this problem, general purpose eigensolvers are not efficient, nor is advisable to resort to the decimation method etc. to obtain the Wiener-Hopf factorization. After reviewing some rigorous understanding of SGF calculation from the perspective of ⊤-PQEP and nonlinear matrix equation, we present our new approach to this problem. In a nutshell, the unit disk where the spectrum of interest lies is broken down adaptively into pieces small enough that they each can be locally tackled by the generalized ⊤-skew-Hamiltonian implicitly restarted shift-and-invert Arnoldi (G⊤SHIRA) algorithm with suitable shifts and other parameters, and the eigenvalues missed by this divide-and-conquer strategy can be recovered thanks to the accurate estimation provided by our newly developed scheme. Notably the novel non-equivalence deflation is proposed to avoid as much as possible duplication of nearby known eigenvalues when a new shift of G⊤SHIRA is determined. We demonstrate our new approach by calculating the SGF of a realistic nanowire whose unit cell is described by a matrix of size 4000 × 4000 at the density functional tight binding level, corresponding to a 8 × 8nm2 cross-section. We believe that quantum transport simulation of realistic nano-devices in the mesoscopic regime will greatly benefit from this work.
Energy functions for regularization algorithms
Delingette, H.; Hebert, M.; Ikeuchi, K.
1991-01-01
Regularization techniques are widely used for inverse problem solving in computer vision such as surface reconstruction, edge detection, or optical flow estimation. Energy functions used for regularization algorithms measure how smooth a curve or surface is, and to render acceptable solutions these energies must verify certain properties such as invariance with Euclidean transformations or invariance with parameterization. The notion of smoothness energy is extended here to the notion of a differential stabilizer, and it is shown that to void the systematic underestimation of undercurvature for planar curve fitting, it is necessary that circles be the curves of maximum smoothness. A set of stabilizers is proposed that meet this condition as well as invariance with rotation and parameterization.
Physical model of dimensional regularization
Energy Technology Data Exchange (ETDEWEB)
Schonfeld, Jonathan F.
2016-12-15
We explicitly construct fractals of dimension 4-ε on which dimensional regularization approximates scalar-field-only quantum-field theory amplitudes. The construction does not require fractals to be Lorentz-invariant in any sense, and we argue that there probably is no Lorentz-invariant fractal of dimension greater than 2. We derive dimensional regularization's power-law screening first for fractals obtained by removing voids from 3-dimensional Euclidean space. The derivation applies techniques from elementary dielectric theory. Surprisingly, fractal geometry by itself does not guarantee the appropriate power-law behavior; boundary conditions at fractal voids also play an important role. We then extend the derivation to 4-dimensional Minkowski space. We comment on generalization to non-scalar fields, and speculate about implications for quantum gravity. (orig.)
Maximum mutual information regularized classification
Wang, Jim Jing-Yan
2014-09-07
In this paper, a novel pattern classification approach is proposed by regularizing the classifier learning to maximize mutual information between the classification response and the true class label. We argue that, with the learned classifier, the uncertainty of the true class label of a data sample should be reduced by knowing its classification response as much as possible. The reduced uncertainty is measured by the mutual information between the classification response and the true class label. To this end, when learning a linear classifier, we propose to maximize the mutual information between classification responses and true class labels of training samples, besides minimizing the classification error and reducing the classifier complexity. An objective function is constructed by modeling mutual information with entropy estimation, and it is optimized by a gradient descend method in an iterative algorithm. Experiments on two real world pattern classification problems show the significant improvements achieved by maximum mutual information regularization.
Maximum mutual information regularized classification
Wang, Jim Jing-Yan; Wang, Yi; Zhao, Shiguang; Gao, Xin
2014-01-01
In this paper, a novel pattern classification approach is proposed by regularizing the classifier learning to maximize mutual information between the classification response and the true class label. We argue that, with the learned classifier, the uncertainty of the true class label of a data sample should be reduced by knowing its classification response as much as possible. The reduced uncertainty is measured by the mutual information between the classification response and the true class label. To this end, when learning a linear classifier, we propose to maximize the mutual information between classification responses and true class labels of training samples, besides minimizing the classification error and reducing the classifier complexity. An objective function is constructed by modeling mutual information with entropy estimation, and it is optimized by a gradient descend method in an iterative algorithm. Experiments on two real world pattern classification problems show the significant improvements achieved by maximum mutual information regularization.
Regularized strings with extrinsic curvature
International Nuclear Information System (INIS)
Ambjoern, J.; Durhuus, B.
1987-07-01
We analyze models of discretized string theories, where the path integral over world sheet variables is regularized by summing over triangulated surfaces. The inclusion of curvature in the action is a necessity for the scaling of the string tension. We discuss the physical properties of models with extrinsic curvature terms in the action and show that the string tension vanishes at the critical point where the bare extrinsic curvature coupling tends to infinity. Similar results are derived for models with intrinsic curvature. (orig.)
Circuit complexity of regular languages
Czech Academy of Sciences Publication Activity Database
Koucký, Michal
2009-01-01
Roč. 45, č. 4 (2009), s. 865-879 ISSN 1432-4350 R&D Projects: GA ČR GP201/07/P276; GA MŠk(CZ) 1M0545 Institutional research plan: CEZ:AV0Z10190503 Keywords : regular languages * circuit complexity * upper and lower bounds Subject RIV: BA - General Mathematics Impact factor: 0.726, year: 2009
General inverse problems for regular variation
DEFF Research Database (Denmark)
Damek, Ewa; Mikosch, Thomas Valentin; Rosinski, Jan
2014-01-01
Regular variation of distributional tails is known to be preserved by various linear transformations of some random structures. An inverse problem for regular variation aims at understanding whether the regular variation of a transformed random object is caused by regular variation of components ...
Cas9-triggered chain ablation of cas9 as a gene drive brake
Wu, Bing; Luo, Liqun; Gao, Xiaojing J.
2016-01-01
With the advent of clustered, regularly interspaced, short palindromic repeats (CRISPR)–CRISPR-associated protein 9 (Cas9) technology, researchers can construct gene drives that can bias the inheritance of edited alleles to alter entire populations. As demonstrated with the mutagenic chain reaction in Drosophila4, the CRISPR-Cas9 system can propagate genomic modification together with the genome-editing machinery itself. Although gene drives might have the potential to control insect-borne di...
Hough, Soren H; Ajetunmobi, Ayokunmi; Brody, Leigh; Humphryes-Kirilov, Neil; Perello, Edward
2016-01-01
Desktop Genetics is a bioinformatics company building a gene-editing platform for personalized medicine. The company works with scientists around the world to design and execute state-of-the-art clustered regularly interspaced short palindromic repeats (CRISPR) experiments. Desktop Genetics feeds the lessons learned about experimental intent, single-guide RNA design and data from international genomics projects into a novel CRISPR artificial intelligence system. We believe that machine learni...
Aydin, Seyid; Personne, Yoann; Newire, Enas; Laverick, Rebecca; Russell, Oliver; Roberts, Adam; Enne, Virve I
2017-01-01
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and their associated cas genes are sequence-specific DNA nuclease systems found in bacteria and archaea. CRISPR/Cas systems use RNA transcripts of previously acquired DNA (spacers) to target invading genetic elements with the same sequence, including plasmids. In this research we studied the relationship between CRISPR/Cas systems and multidrug resistance in Escherichia coli . The presence of Type I-E and Type I-F CRISPR syste...
Park, Joo Youn; Moon, Bo Youn; Park, Juw Won; Thornton, Justin A.; Park, Yong Ho; Seo, Keun Seok
2017-01-01
Discovery of clustered, regularly interspaced, short palindromic repeats and the Cas9 RNA-guided nuclease (CRISPR/Cas9) system provides a new opportunity to create programmable gene-specific antimicrobials that are far less likely to drive resistance than conventional antibiotics. However, the practical therapeutic use of CRISPR/Cas9 is still questionable due to current shortcomings in phage-based delivery systems such as inefficient delivery, narrow host range, and potential transfer of viru...
Price, Valerie J.; Huo, Wenwen; Sharifi, Ardalan; Palmer, Kelli L.
2016-01-01
ABSTRACT Enterococcus faecalis is an opportunistic pathogen and a leading cause of nosocomial infections. Conjugative pheromone-responsive plasmids are narrow-host-range mobile genetic elements (MGEs) that are rapid disseminators of antibiotic resistance in the faecalis species. Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification confer acquired and innate immunity, respectively, against MGE acquisition in bacteria. Most multidrug-resistant E.?fa...
Diop, Awa; Diop, Khoudia; Tomei, Enora; Raoult, Didier; Fenollar, Florence; Fournier, Pierre-Edouard
2018-03-01
We report here the draft genome sequence of Ezakiella peruensis strain M6.X2 T The draft genome is 1,672,788 bp long and harbors 1,589 predicted protein-encoding genes, including 26 antibiotic resistance genes with 1 gene encoding vancomycin resistance. The genome also exhibits 1 clustered regularly interspaced short palindromic repeat region and 333 genes acquired by horizontal gene transfer. Copyright © 2018 Diop et al.
System-level perturbations of cell metabolism using CRISPR/Cas9
DEFF Research Database (Denmark)
Jakociunas, Tadas; Jensen, Michael Krogh; Keasling, Jay
2017-01-01
CRISPR/Cas9 (clustered regularly interspaced palindromic repeats and the associated protein Cas9) techniques have made genome engineering and transcriptional reprogramming studies more advanced and cost-effective. For metabolic engineering purposes, the CRISPR-based tools have been applied...... previously possible. In this mini-review we highlight recent studies adopting CRISPR/Cas9 for systems-level perturbations and model-guided metabolic engineering....
CRISPR-Cpf1: A New Tool for Plant Genome Editing
Zaidi, Syed Shan-e-Ali
2017-05-19
Clustered regularly interspaced palindromic repeats (CRISPR)-CRISPR-associated proteins (CRISPR-Cas), a groundbreaking genome-engineering tool, has facilitated targeted trait improvement in plants. Recently, CRISPR-CRISPR from Prevotella and Francisella 1 (Cpf1) has emerged as a new tool for efficient genome editing, including DNA-free editing in plants, with higher efficiency, specificity, and potentially wider applications than CRISPR-Cas9.
CRISPR-Cpf1: A New Tool for Plant Genome Editing
Zaidi, Syed Shan-e-Ali; Mahfouz, Magdy M.; Mansoor, Shahid
2017-01-01
Clustered regularly interspaced palindromic repeats (CRISPR)-CRISPR-associated proteins (CRISPR-Cas), a groundbreaking genome-engineering tool, has facilitated targeted trait improvement in plants. Recently, CRISPR-CRISPR from Prevotella and Francisella 1 (Cpf1) has emerged as a new tool for efficient genome editing, including DNA-free editing in plants, with higher efficiency, specificity, and potentially wider applications than CRISPR-Cas9.
The genetic engineering system, clustered regularly interspaced short palindromic repeats (CRISPR), has conventionally been used to inactivate genes by making targeted double stranded cuts in DNA. While CRISPR is a useful tool, it can only be used to create loss-of-function modifications and often causes off-target effects due to the disruptive mechanism by which it works. CTD2 researchers at the University of California, San Francisco recently addressed these shortcomings in a publication in Cell.
Guan, Jing; Wang, Wanying; Sun, Baolin
2017-01-01
ABSTRACT CRISPR-Cas (clustered regularly interspaced short palindromic repeat [CRISPR]-CRISPR-associated protein [Cas]) systems can provide protection against invading genetic elements by using CRISPR RNAs (crRNAs) as a guide to locate and degrade the target DNA. CRISPR-Cas systems have been classified into two classes and five types according to the content of cas genes. Previous studies have indicated that CRISPR-Cas systems can avoid viral infection and block plasmid transfer. Here we show...
Regularized Statistical Analysis of Anatomy
DEFF Research Database (Denmark)
Sjöstrand, Karl
2007-01-01
This thesis presents the application and development of regularized methods for the statistical analysis of anatomical structures. Focus is on structure-function relationships in the human brain, such as the connection between early onset of Alzheimer’s disease and shape changes of the corpus...... and mind. Statistics represents a quintessential part of such investigations as they are preluded by a clinical hypothesis that must be verified based on observed data. The massive amounts of image data produced in each examination pose an important and interesting statistical challenge...... efficient algorithms which make the analysis of large data sets feasible, and gives examples of applications....
Regularization methods in Banach spaces
Schuster, Thomas; Hofmann, Bernd; Kazimierski, Kamil S
2012-01-01
Regularization methods aimed at finding stable approximate solutions are a necessary tool to tackle inverse and ill-posed problems. Usually the mathematical model of an inverse problem consists of an operator equation of the first kind and often the associated forward operator acts between Hilbert spaces. However, for numerous problems the reasons for using a Hilbert space setting seem to be based rather on conventions than on an approprimate and realistic model choice, so often a Banach space setting would be closer to reality. Furthermore, sparsity constraints using general Lp-norms or the B
Academic Training Lecture - Regular Programme
PH Department
2011-01-01
Regular Lecture Programme 9 May 2011 ACT Lectures on Detectors - Inner Tracking Detectors by Pippa Wells (CERN) 10 May 2011 ACT Lectures on Detectors - Calorimeters (2/5) by Philippe Bloch (CERN) 11 May 2011 ACT Lectures on Detectors - Muon systems (3/5) by Kerstin Hoepfner (RWTH Aachen) 12 May 2011 ACT Lectures on Detectors - Particle Identification and Forward Detectors by Peter Krizan (University of Ljubljana and J. Stefan Institute, Ljubljana, Slovenia) 13 May 2011 ACT Lectures on Detectors - Trigger and Data Acquisition (5/5) by Dr. Brian Petersen (CERN) from 11:00 to 12:00 at CERN ( Bldg. 222-R-001 - Filtration Plant )
RES: Regularized Stochastic BFGS Algorithm
Mokhtari, Aryan; Ribeiro, Alejandro
2014-12-01
RES, a regularized stochastic version of the Broyden-Fletcher-Goldfarb-Shanno (BFGS) quasi-Newton method is proposed to solve convex optimization problems with stochastic objectives. The use of stochastic gradient descent algorithms is widespread, but the number of iterations required to approximate optimal arguments can be prohibitive in high dimensional problems. Application of second order methods, on the other hand, is impracticable because computation of objective function Hessian inverses incurs excessive computational cost. BFGS modifies gradient descent by introducing a Hessian approximation matrix computed from finite gradient differences. RES utilizes stochastic gradients in lieu of deterministic gradients for both, the determination of descent directions and the approximation of the objective function's curvature. Since stochastic gradients can be computed at manageable computational cost RES is realizable and retains the convergence rate advantages of its deterministic counterparts. Convergence results show that lower and upper bounds on the Hessian egeinvalues of the sample functions are sufficient to guarantee convergence to optimal arguments. Numerical experiments showcase reductions in convergence time relative to stochastic gradient descent algorithms and non-regularized stochastic versions of BFGS. An application of RES to the implementation of support vector machines is developed.
Regularized Label Relaxation Linear Regression.
Fang, Xiaozhao; Xu, Yong; Li, Xuelong; Lai, Zhihui; Wong, Wai Keung; Fang, Bingwu
2018-04-01
Linear regression (LR) and some of its variants have been widely used for classification problems. Most of these methods assume that during the learning phase, the training samples can be exactly transformed into a strict binary label matrix, which has too little freedom to fit the labels adequately. To address this problem, in this paper, we propose a novel regularized label relaxation LR method, which has the following notable characteristics. First, the proposed method relaxes the strict binary label matrix into a slack variable matrix by introducing a nonnegative label relaxation matrix into LR, which provides more freedom to fit the labels and simultaneously enlarges the margins between different classes as much as possible. Second, the proposed method constructs the class compactness graph based on manifold learning and uses it as the regularization item to avoid the problem of overfitting. The class compactness graph is used to ensure that the samples sharing the same labels can be kept close after they are transformed. Two different algorithms, which are, respectively, based on -norm and -norm loss functions are devised. These two algorithms have compact closed-form solutions in each iteration so that they are easily implemented. Extensive experiments show that these two algorithms outperform the state-of-the-art algorithms in terms of the classification accuracy and running time.
From inactive to regular jogger
DEFF Research Database (Denmark)
Lund-Cramer, Pernille; Brinkmann Løite, Vibeke; Bredahl, Thomas Viskum Gjelstrup
study was conducted using individual semi-structured interviews on how a successful long-term behavior change had been achieved. Ten informants were purposely selected from participants in the DANO-RUN research project (7 men, 3 women, average age 41.5). Interviews were performed on the basis of Theory...... of Planned Behavior (TPB) and The Transtheoretical Model (TTM). Coding and analysis of interviews were performed using NVivo 10 software. Results TPB: During the behavior change process, the intention to jogging shifted from a focus on weight loss and improved fitness to both physical health, psychological......Title From inactive to regular jogger - a qualitative study of achieved behavioral change among recreational joggers Authors Pernille Lund-Cramer & Vibeke Brinkmann Løite Purpose Despite extensive knowledge of barriers to physical activity, most interventions promoting physical activity have proven...
Tessellating the Sphere with Regular Polygons
Soto-Johnson, Hortensia; Bechthold, Dawn
2004-01-01
Tessellations in the Euclidean plane and regular polygons that tessellate the sphere are reviewed. The regular polygons that can possibly tesellate the sphere are spherical triangles, squares and pentagons.
On the equivalence of different regularization methods
International Nuclear Information System (INIS)
Brzezowski, S.
1985-01-01
The R-circunflex-operation preceded by the regularization procedure is discussed. Some arguments are given, according to which the results may depend on the method of regularization, introduced in order to avoid divergences in perturbation calculations. 10 refs. (author)
The uniqueness of the regularization procedure
International Nuclear Information System (INIS)
Brzezowski, S.
1981-01-01
On the grounds of the BPHZ procedure, the criteria of correct regularization in perturbation calculations of QFT are given, together with the prescription for dividing the regularized formulas into the finite and infinite parts. (author)
Tucker, Colin; McHugh, Theresa A.; Howell, Armin; Gill, Richard; Weber, Bettina; Belnap, Jayne; Grote, Ed; Reed, Sasha C.
2017-01-01
Carbon cycling associated with biological soil crusts, which occupy interspaces between vascular plants in drylands globally, may be an important part of the coupled climate-carbon cycle of the Earth system. A major challenge to understanding CO2 fluxes in these systems is that much of the biotic and biogeochemical activity occurs in the upper few mm of the soil surface layer (i.e., the ‘mantle of fertility’), which exhibits highly dynamic and difficult to measure temperature and moisture fluctuations. Here, we report a multi-sensor approach to simultaneously measuring temperature and moisture of this biocrust surface layer (0–2 mm), and the deeper soil profile, concurrent with automated measurement of surface soil CO2effluxes. Our results illuminate robust relationships between biocrust water content and field CO2 pulses that have previously been difficult to detect and explain. All observed CO2 pulses over the measurement period corresponded to surface wetting events, including when the wetting events did not penetrate into the soil below the biocrust layer (0–2 mm). The variability of temperature and moisture of the biocrust surface layer was much greater than even in the 0–5 cm layer of the soil beneath the biocrust, or deeper in the soil profile. We therefore suggest that coupling surface measurements of biocrust moisture and temperature to automated CO2flux measurements may greatly improve our understanding of the climatic sensitivity of carbon cycling in biocrusted interspaces in our study region, and that this method may be globally relevant and applicable.
Application of Turchin's method of statistical regularization
Zelenyi, Mikhail; Poliakova, Mariia; Nozik, Alexander; Khudyakov, Alexey
2018-04-01
During analysis of experimental data, one usually needs to restore a signal after it has been convoluted with some kind of apparatus function. According to Hadamard's definition this problem is ill-posed and requires regularization to provide sensible results. In this article we describe an implementation of the Turchin's method of statistical regularization based on the Bayesian approach to the regularization strategy.
Regular extensions of some classes of grammars
Nijholt, Antinus
Culik and Cohen introduced the class of LR-regular grammars, an extension of the LR(k) grammars. In this report we consider the analogous extension of the LL(k) grammers, called the LL-regular grammars. The relations of this class of grammars to other classes of grammars are shown. Every LL-regular
Willwand, Kurt; Moroianu, Adela; Hörlein, Rita; Stremmel, Wolfgang; Rommelaere, Jean
2002-07-01
The linear single-stranded DNA genome of minute virus of mice (MVM) is replicated via a double-stranded replicative form (RF) intermediate DNA. Amplification of viral RF DNA requires the structural transition of the right-end palindrome from a linear duplex into a double-hairpin structure, which serves for the repriming of unidirectional DNA synthesis. This conformational transition was found previously to be induced by the MVM nonstructural protein NS1. Elimination of the cognate NS1-binding sites, [ACCA](2), from the central region of the right-end palindrome next to the axis of symmetry was shown to markedly reduce the efficiency of hairpin-primed DNA replication, as measured in a reconstituted in vitro replication system. Thus, [ACCA](2) sequence motifs are essential as NS1-binding elements in the context of the structural transition of the right-end MVM palindrome.
Class of regular bouncing cosmologies
Vasilić, Milovan
2017-06-01
In this paper, I construct a class of everywhere regular geometric sigma models that possess bouncing solutions. Precisely, I show that every bouncing metric can be made a solution of such a model. My previous attempt to do so by employing one scalar field has failed due to the appearance of harmful singularities near the bounce. In this work, I use four scalar fields to construct a class of geometric sigma models which are free of singularities. The models within the class are parametrized by their background geometries. I prove that, whatever background is chosen, the dynamics of its small perturbations is classically stable on the whole time axis. Contrary to what one expects from the structure of the initial Lagrangian, the physics of background fluctuations is found to carry two tensor, two vector, and two scalar degrees of freedom. The graviton mass, which naturally appears in these models, is shown to be several orders of magnitude smaller than its experimental bound. I provide three simple examples to demonstrate how this is done in practice. In particular, I show that graviton mass can be made arbitrarily small.
Adaptive regularization of noisy linear inverse problems
DEFF Research Database (Denmark)
Hansen, Lars Kai; Madsen, Kristoffer Hougaard; Lehn-Schiøler, Tue
2006-01-01
In the Bayesian modeling framework there is a close relation between regularization and the prior distribution over parameters. For prior distributions in the exponential family, we show that the optimal hyper-parameter, i.e., the optimal strength of regularization, satisfies a simple relation: T......: The expectation of the regularization function, i.e., takes the same value in the posterior and prior distribution. We present three examples: two simulations, and application in fMRI neuroimaging....
Higher derivative regularization and chiral anomaly
International Nuclear Information System (INIS)
Nagahama, Yoshinori.
1985-02-01
A higher derivative regularization which automatically leads to the consistent chiral anomaly is analyzed in detail. It explicitly breaks all the local gauge symmetry but preserves global chiral symmetry and leads to the chirally symmetric consistent anomaly. This regularization thus clarifies the physics content contained in the consistent anomaly. We also briefly comment on the application of this higher derivative regularization to massless QED. (author)
Regularity effect in prospective memory during aging
Directory of Open Access Journals (Sweden)
Geoffrey Blondelle
2016-10-01
Full Text Available Background: Regularity effect can affect performance in prospective memory (PM, but little is known on the cognitive processes linked to this effect. Moreover, its impacts with regard to aging remain unknown. To our knowledge, this study is the first to examine regularity effect in PM in a lifespan perspective, with a sample of young, intermediate, and older adults. Objective and design: Our study examined the regularity effect in PM in three groups of participants: 28 young adults (18–30, 16 intermediate adults (40–55, and 25 older adults (65–80. The task, adapted from the Virtual Week, was designed to manipulate the regularity of the various activities of daily life that were to be recalled (regular repeated activities vs. irregular non-repeated activities. We examine the role of several cognitive functions including certain dimensions of executive functions (planning, inhibition, shifting, and binding, short-term memory, and retrospective episodic memory to identify those involved in PM, according to regularity and age. Results: A mixed-design ANOVA showed a main effect of task regularity and an interaction between age and regularity: an age-related difference in PM performances was found for irregular activities (older < young, but not for regular activities. All participants recalled more regular activities than irregular ones with no age effect. It appeared that recalling of regular activities only involved planning for both intermediate and older adults, while recalling of irregular ones were linked to planning, inhibition, short-term memory, binding, and retrospective episodic memory. Conclusion: Taken together, our data suggest that planning capacities seem to play a major role in remembering to perform intended actions with advancing age. Furthermore, the age-PM-paradox may be attenuated when the experimental design is adapted by implementing a familiar context through the use of activities of daily living. The clinical
Regularity effect in prospective memory during aging
Blondelle, Geoffrey; Hainselin, Mathieu; Gounden, Yannick; Heurley, Laurent; Voisin, Hélène; Megalakaki, Olga; Bressous, Estelle; Quaglino, Véronique
2016-01-01
Background: Regularity effect can affect performance in prospective memory (PM), but little is known on the cognitive processes linked to this effect. Moreover, its impacts with regard to aging remain unknown. To our knowledge, this study is the first to examine regularity effect in PM in a lifespan perspective, with a sample of young, intermediate, and older adults.Objective and design: Our study examined the regularity effect in PM in three groups of participants: 28 young adults (18–30), 1...
Regularization and error assignment to unfolded distributions
Zech, Gunter
2011-01-01
The commonly used approach to present unfolded data only in graphical formwith the diagonal error depending on the regularization strength is unsatisfac-tory. It does not permit the adjustment of parameters of theories, the exclusionof theories that are admitted by the observed data and does not allow the com-bination of data from different experiments. We propose fixing the regulariza-tion strength by a p-value criterion, indicating the experimental uncertaintiesindependent of the regularization and publishing the unfolded data in additionwithout regularization. These considerations are illustrated with three differentunfolding and smoothing approaches applied to a toy example.
Iterative Regularization with Minimum-Residual Methods
DEFF Research Database (Denmark)
Jensen, Toke Koldborg; Hansen, Per Christian
2007-01-01
subspaces. We provide a combination of theory and numerical examples, and our analysis confirms the experience that MINRES and MR-II can work as general regularization methods. We also demonstrate theoretically and experimentally that the same is not true, in general, for GMRES and RRGMRES their success......We study the regularization properties of iterative minimum-residual methods applied to discrete ill-posed problems. In these methods, the projection onto the underlying Krylov subspace acts as a regularizer, and the emphasis of this work is on the role played by the basis vectors of these Krylov...... as regularization methods is highly problem dependent....
Iterative regularization with minimum-residual methods
DEFF Research Database (Denmark)
Jensen, Toke Koldborg; Hansen, Per Christian
2006-01-01
subspaces. We provide a combination of theory and numerical examples, and our analysis confirms the experience that MINRES and MR-II can work as general regularization methods. We also demonstrate theoretically and experimentally that the same is not true, in general, for GMRES and RRGMRES - their success......We study the regularization properties of iterative minimum-residual methods applied to discrete ill-posed problems. In these methods, the projection onto the underlying Krylov subspace acts as a regularizer, and the emphasis of this work is on the role played by the basis vectors of these Krylov...... as regularization methods is highly problem dependent....
International Nuclear Information System (INIS)
Baburajendran, Nithya; Palasingam, Paaventhan; Ng, Calista Keow Leng; Jauch, Ralf; Kolatkar, Prasanna R.
2009-01-01
Crystals of palindromic SBE DNA-bound Smad1 MH1 domain diffracting to 2.7 Å resolution have been obtained. The bone morphogenetic protein (BMP) signalling pathway regulates diverse processes such as cell differentiation, anterior/posterior axis specification, cell growth and the formation of extra-embryonic tissues. The transcription factor Smad1 relays the BMP signal from the cytoplasm to the nucleus, where it binds short DNA-sequence motifs and regulates gene expression. However, how Smad1 selectively targets particular genomic regions is poorly understood. In order to understand the physical basis of the specific interaction of Smad1 with DNA and to contrast it with the highly homologous but functionally distinct Smad3 protein, the DNA-binding Mad-homology 1 (MH1) domain of Smad1 was cocrystallized with a 17-mer palindromic Smad-binding element (SBE). The extensive optimizations of the length, binding-site spacing and terminal sequences of the DNA element in combination with the other crystallization parameters necessary for obtaining diffraction-quality crystals are described here. A 2.7 Å resolution native data set was collected at the National Synchrotron Radiation Research Centre, Taiwan, from crystals grown in a solution containing 0.2 M ammonium tartrate dibasic, 20% PEG 3350, 3% 2-propanol and 10% glycerol. The data set was indexed and merged in space group P222, with unit-cell parameters a = 73.94, b = 77.49, c = 83.78 Å, α = β = γ = 90°. The solvent content in the unit cell is consistent with the presence of two Smad1 MH1 molecules bound to the duplex DNA in the asymmetric unit
Directory of Open Access Journals (Sweden)
Massimo Giangaspero
2008-06-01
Full Text Available Forty-three strains of classical swine fever (hog cholera virus (CSFV from outbreaks in pigs in Europe, Asia and America, two strains from commercial CSFV modified live vaccines and a strain isolated from a diseased lamb from Spain were subjected to analyses of nucleotide sequence variations in the 5’ terminal region of the genome. These isolates were divided into three clusters, namely: CSFV-1, CSFV-2, and CSFV-3, based on palindromic nucleotide substitutions in the 5’ untranslated region (UTR. The homology degree, according to nucleotide base pairing variation in the secondary palindromic structure of the three variable loci V1, V2 and V3, was 60% in the CSFV species, with a mean divergence value of 6.19 base pairs (bp. relatedness within genotypes ranged from 71.11% to 100%, with mean divergence values from 5.5 to 0.73 base pairs. Subgenotypes showed a divergence ranging from 1 to 9 base pairs within the genotype. Genotype CSFV-1 revealed 15 base pair combinations with 13 divergent base pairs, resulting in 4 subgenotypes with 6 variants in subgenotype CSFV-1.1, including the reference strain Brescia and 6 variants in subgenotype CSFV-1.2, including the Alfort reference strain. Subgenotypes CSFV-1.3 and CSFV-1.4 comprised one and two variants, respectively. Genotype CSFV-2 was represented by the Spanish ovine isolate 5440/99 and the genotype CSFV-3 included the Japanese strains Okinawa/86 and Kanagawa/74. CSFV genotypes revealed a strong relationship with Border disease virus strains, showing relatively low divergence values when compared to other pestivirus species. Evaluation of nucleotide base pair divergence among genotypes and expression of evolutionary changes in the CSFV species led to the construction of a phylogenetic tree based on secondary structure.
A regularized stationary mean-field game
Yang, Xianjin
2016-01-01
In the thesis, we discuss the existence and numerical approximations of solutions of a regularized mean-field game with a low-order regularization. In the first part, we prove a priori estimates and use the continuation method to obtain the existence of a solution with a positive density. Finally, we introduce the monotone flow method and solve the system numerically.
A regularized stationary mean-field game
Yang, Xianjin
2016-04-19
In the thesis, we discuss the existence and numerical approximations of solutions of a regularized mean-field game with a low-order regularization. In the first part, we prove a priori estimates and use the continuation method to obtain the existence of a solution with a positive density. Finally, we introduce the monotone flow method and solve the system numerically.
On infinite regular and chiral maps
Arredondo, John A.; Valdez, Camilo Ramírez y Ferrán
2015-01-01
We prove that infinite regular and chiral maps take place on surfaces with at most one end. Moreover, we prove that an infinite regular or chiral map on an orientable surface with genus can only be realized on the Loch Ness monster, that is, the topological surface of infinite genus with one end.
From recreational to regular drug use
DEFF Research Database (Denmark)
Järvinen, Margaretha; Ravn, Signe
2011-01-01
This article analyses the process of going from recreational use to regular and problematic use of illegal drugs. We present a model containing six career contingencies relevant for young people’s progress from recreational to regular drug use: the closing of social networks, changes in forms...
Automating InDesign with Regular Expressions
Kahrel, Peter
2006-01-01
If you need to make automated changes to InDesign documents beyond what basic search and replace can handle, you need regular expressions, and a bit of scripting to make them work. This Short Cut explains both how to write regular expressions, so you can find and replace the right things, and how to use them in InDesign specifically.
Regularization modeling for large-eddy simulation
Geurts, Bernardus J.; Holm, D.D.
2003-01-01
A new modeling approach for large-eddy simulation (LES) is obtained by combining a "regularization principle" with an explicit filter and its inversion. This regularization approach allows a systematic derivation of the implied subgrid model, which resolves the closure problem. The central role of
2010-07-01
... employee under subsection (a) or in excess of the employee's normal working hours or regular working hours... Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR STATEMENTS OF GENERAL POLICY OR... not less than one and one-half times their regular rates of pay. Section 7(e) of the Act defines...
Lee, H. W.; Lim, H. W.; Jeon, D. H.; Park, C. K.; Cho, H. S.; Seo, C. W.; Lee, D. Y.; Kim, K. S.; Kim, G. A.; Park, S. Y.; Kang, S. Y.; Park, J. E.; Kim, W. S.; Woo, T. H.; Oh, J. E.
2018-06-01
This study investigated the effectiveness of a new method for measuring the actual focal spot position of a diagnostic x-ray tube using a high-precision antiscatter grid and a digital x-ray detector in which grid magnification, which is directly related to the focal spot position, was determined from the Fourier spectrum of the acquired x-ray grid’s image. A systematic experiment was performed to demonstrate the viability of the proposed measurement method. The hardware system used in the experiment consisted of an x-ray tube run at 50 kVp and 1 mA, a flat-panel detector with a pixel size of 49.5 µm, and a high-precision carbon-interspaced grid with a strip density of 200 lines/inch. The results indicated that the focal spot of the x-ray tube (Jupiter 5000, Oxford Instruments) used in the experiment was located approximately 31.10 mm inside from the exit flange, well agreed with the nominal value of 31.05 mm, which demonstrates the viability of the proposed measurement method. Thus, the proposed method can be utilized for system’s performance optimization in many x-ray imaging applications.
An iterative method for Tikhonov regularization with a general linear regularization operator
Hochstenbach, M.E.; Reichel, L.
2010-01-01
Tikhonov regularization is one of the most popular approaches to solve discrete ill-posed problems with error-contaminated data. A regularization operator and a suitable value of a regularization parameter have to be chosen. This paper describes an iterative method, based on Golub-Kahan
Multiple graph regularized protein domain ranking
Wang, Jim Jing-Yan
2012-11-19
Background: Protein domain ranking is a fundamental task in structural biology. Most protein domain ranking methods rely on the pairwise comparison of protein domains while neglecting the global manifold structure of the protein domain database. Recently, graph regularized ranking that exploits the global structure of the graph defined by the pairwise similarities has been proposed. However, the existing graph regularized ranking methods are very sensitive to the choice of the graph model and parameters, and this remains a difficult problem for most of the protein domain ranking methods.Results: To tackle this problem, we have developed the Multiple Graph regularized Ranking algorithm, MultiG-Rank. Instead of using a single graph to regularize the ranking scores, MultiG-Rank approximates the intrinsic manifold of protein domain distribution by combining multiple initial graphs for the regularization. Graph weights are learned with ranking scores jointly and automatically, by alternately minimizing an objective function in an iterative algorithm. Experimental results on a subset of the ASTRAL SCOP protein domain database demonstrate that MultiG-Rank achieves a better ranking performance than single graph regularized ranking methods and pairwise similarity based ranking methods.Conclusion: The problem of graph model and parameter selection in graph regularized protein domain ranking can be solved effectively by combining multiple graphs. This aspect of generalization introduces a new frontier in applying multiple graphs to solving protein domain ranking applications. 2012 Wang et al; licensee BioMed Central Ltd.
Multiple graph regularized protein domain ranking
Wang, Jim Jing-Yan; Bensmail, Halima; Gao, Xin
2012-01-01
Background: Protein domain ranking is a fundamental task in structural biology. Most protein domain ranking methods rely on the pairwise comparison of protein domains while neglecting the global manifold structure of the protein domain database. Recently, graph regularized ranking that exploits the global structure of the graph defined by the pairwise similarities has been proposed. However, the existing graph regularized ranking methods are very sensitive to the choice of the graph model and parameters, and this remains a difficult problem for most of the protein domain ranking methods.Results: To tackle this problem, we have developed the Multiple Graph regularized Ranking algorithm, MultiG-Rank. Instead of using a single graph to regularize the ranking scores, MultiG-Rank approximates the intrinsic manifold of protein domain distribution by combining multiple initial graphs for the regularization. Graph weights are learned with ranking scores jointly and automatically, by alternately minimizing an objective function in an iterative algorithm. Experimental results on a subset of the ASTRAL SCOP protein domain database demonstrate that MultiG-Rank achieves a better ranking performance than single graph regularized ranking methods and pairwise similarity based ranking methods.Conclusion: The problem of graph model and parameter selection in graph regularized protein domain ranking can be solved effectively by combining multiple graphs. This aspect of generalization introduces a new frontier in applying multiple graphs to solving protein domain ranking applications. 2012 Wang et al; licensee BioMed Central Ltd.
Hierarchical regular small-world networks
International Nuclear Information System (INIS)
Boettcher, Stefan; Goncalves, Bruno; Guclu, Hasan
2008-01-01
Two new networks are introduced that resemble small-world properties. These networks are recursively constructed but retain a fixed, regular degree. They possess a unique one-dimensional lattice backbone overlaid by a hierarchical sequence of long-distance links, mixing real-space and small-world features. Both networks, one 3-regular and the other 4-regular, lead to distinct behaviors, as revealed by renormalization group studies. The 3-regular network is planar, has a diameter growing as √N with system size N, and leads to super-diffusion with an exact, anomalous exponent d w = 1.306..., but possesses only a trivial fixed point T c = 0 for the Ising ferromagnet. In turn, the 4-regular network is non-planar, has a diameter growing as ∼2 √(log 2 N 2 ) , exhibits 'ballistic' diffusion (d w = 1), and a non-trivial ferromagnetic transition, T c > 0. It suggests that the 3-regular network is still quite 'geometric', while the 4-regular network qualifies as a true small world with mean-field properties. As an engineering application we discuss synchronization of processors on these networks. (fast track communication)
Multiple graph regularized protein domain ranking.
Wang, Jim Jing-Yan; Bensmail, Halima; Gao, Xin
2012-11-19
Protein domain ranking is a fundamental task in structural biology. Most protein domain ranking methods rely on the pairwise comparison of protein domains while neglecting the global manifold structure of the protein domain database. Recently, graph regularized ranking that exploits the global structure of the graph defined by the pairwise similarities has been proposed. However, the existing graph regularized ranking methods are very sensitive to the choice of the graph model and parameters, and this remains a difficult problem for most of the protein domain ranking methods. To tackle this problem, we have developed the Multiple Graph regularized Ranking algorithm, MultiG-Rank. Instead of using a single graph to regularize the ranking scores, MultiG-Rank approximates the intrinsic manifold of protein domain distribution by combining multiple initial graphs for the regularization. Graph weights are learned with ranking scores jointly and automatically, by alternately minimizing an objective function in an iterative algorithm. Experimental results on a subset of the ASTRAL SCOP protein domain database demonstrate that MultiG-Rank achieves a better ranking performance than single graph regularized ranking methods and pairwise similarity based ranking methods. The problem of graph model and parameter selection in graph regularized protein domain ranking can be solved effectively by combining multiple graphs. This aspect of generalization introduces a new frontier in applying multiple graphs to solving protein domain ranking applications.
Coupling regularizes individual units in noisy populations
International Nuclear Information System (INIS)
Ly Cheng; Ermentrout, G. Bard
2010-01-01
The regularity of a noisy system can modulate in various ways. It is well known that coupling in a population can lower the variability of the entire network; the collective activity is more regular. Here, we show that diffusive (reciprocal) coupling of two simple Ornstein-Uhlenbeck (O-U) processes can regularize the individual, even when it is coupled to a noisier process. In cellular networks, the regularity of individual cells is important when a select few play a significant role. The regularizing effect of coupling surprisingly applies also to general nonlinear noisy oscillators. However, unlike with the O-U process, coupling-induced regularity is robust to different kinds of coupling. With two coupled noisy oscillators, we derive an asymptotic formula assuming weak noise and coupling for the variance of the period (i.e., spike times) that accurately captures this effect. Moreover, we find that reciprocal coupling can regularize the individual period of higher dimensional oscillators such as the Morris-Lecar and Brusselator models, even when coupled to noisier oscillators. Coupling can have a counterintuitive and beneficial effect on noisy systems. These results have implications for the role of connectivity with noisy oscillators and the modulation of variability of individual oscillators.
Multiple graph regularized protein domain ranking
Directory of Open Access Journals (Sweden)
Wang Jim
2012-11-01
Full Text Available Abstract Background Protein domain ranking is a fundamental task in structural biology. Most protein domain ranking methods rely on the pairwise comparison of protein domains while neglecting the global manifold structure of the protein domain database. Recently, graph regularized ranking that exploits the global structure of the graph defined by the pairwise similarities has been proposed. However, the existing graph regularized ranking methods are very sensitive to the choice of the graph model and parameters, and this remains a difficult problem for most of the protein domain ranking methods. Results To tackle this problem, we have developed the Multiple Graph regularized Ranking algorithm, MultiG-Rank. Instead of using a single graph to regularize the ranking scores, MultiG-Rank approximates the intrinsic manifold of protein domain distribution by combining multiple initial graphs for the regularization. Graph weights are learned with ranking scores jointly and automatically, by alternately minimizing an objective function in an iterative algorithm. Experimental results on a subset of the ASTRAL SCOP protein domain database demonstrate that MultiG-Rank achieves a better ranking performance than single graph regularized ranking methods and pairwise similarity based ranking methods. Conclusion The problem of graph model and parameter selection in graph regularized protein domain ranking can be solved effectively by combining multiple graphs. This aspect of generalization introduces a new frontier in applying multiple graphs to solving protein domain ranking applications.
Diagrammatic methods in phase-space regularization
International Nuclear Information System (INIS)
Bern, Z.; Halpern, M.B.; California Univ., Berkeley
1987-11-01
Using the scalar prototype and gauge theory as the simplest possible examples, diagrammatic methods are developed for the recently proposed phase-space form of continuum regularization. A number of one-loop and all-order applications are given, including general diagrammatic discussions of the nogrowth theorem and the uniqueness of the phase-space stochastic calculus. The approach also generates an alternate derivation of the equivalence of the large-β phase-space regularization to the more conventional coordinate-space regularization. (orig.)
J-regular rings with injectivities
Shen, Liang
2010-01-01
A ring $R$ is called a J-regular ring if R/J(R) is von Neumann regular, where J(R) is the Jacobson radical of R. It is proved that if R is J-regular, then (i) R is right n-injective if and only if every homomorphism from an $n$-generated small right ideal of $R$ to $R_{R}$ can be extended to one from $R_{R}$ to $R_{R}$; (ii) R is right FP-injective if and only if R is right (J, R)-FP-injective. Some known results are improved.
Generalized regular genus for manifolds with boundary
Directory of Open Access Journals (Sweden)
Paola Cristofori
2003-05-01
Full Text Available We introduce a generalization of the regular genus, a combinatorial invariant of PL manifolds ([10], which is proved to be strictly related, in dimension three, to generalized Heegaard splittings defined in [12].
Geometric regularizations and dual conifold transitions
International Nuclear Information System (INIS)
Landsteiner, Karl; Lazaroiu, Calin I.
2003-01-01
We consider a geometric regularization for the class of conifold transitions relating D-brane systems on noncompact Calabi-Yau spaces to certain flux backgrounds. This regularization respects the SL(2,Z) invariance of the flux superpotential, and allows for computation of the relevant periods through the method of Picard-Fuchs equations. The regularized geometry is a noncompact Calabi-Yau which can be viewed as a monodromic fibration, with the nontrivial monodromy being induced by the regulator. It reduces to the original, non-monodromic background when the regulator is removed. Using this regularization, we discuss the simple case of the local conifold, and show how the relevant field-theoretic information can be extracted in this approach. (author)
Fast and compact regular expression matching
DEFF Research Database (Denmark)
Bille, Philip; Farach-Colton, Martin
2008-01-01
We study 4 problems in string matching, namely, regular expression matching, approximate regular expression matching, string edit distance, and subsequence indexing, on a standard word RAM model of computation that allows logarithmic-sized words to be manipulated in constant time. We show how...... to improve the space and/or remove a dependency on the alphabet size for each problem using either an improved tabulation technique of an existing algorithm or by combining known algorithms in a new way....
Regular-fat dairy and human health
DEFF Research Database (Denmark)
Astrup, Arne; Bradley, Beth H Rice; Brenna, J Thomas
2016-01-01
In recent history, some dietary recommendations have treated dairy fat as an unnecessary source of calories and saturated fat in the human diet. These assumptions, however, have recently been brought into question by current research on regular fat dairy products and human health. In an effort to......, cheese and yogurt, can be important components of an overall healthy dietary pattern. Systematic examination of the effects of dietary patterns that include regular-fat milk, cheese and yogurt on human health is warranted....
Deterministic automata for extended regular expressions
Directory of Open Access Journals (Sweden)
Syzdykov Mirzakhmet
2017-12-01
Full Text Available In this work we present the algorithms to produce deterministic finite automaton (DFA for extended operators in regular expressions like intersection, subtraction and complement. The method like “overriding” of the source NFA(NFA not defined with subset construction rules is used. The past work described only the algorithm for AND-operator (or intersection of regular languages; in this paper the construction for the MINUS-operator (and complement is shown.
Regularities of intermediate adsorption complex relaxation
International Nuclear Information System (INIS)
Manukova, L.A.
1982-01-01
The experimental data, characterizing the regularities of intermediate adsorption complex relaxation in the polycrystalline Mo-N 2 system at 77 K are given. The method of molecular beam has been used in the investigation. The analytical expressions of change regularity in the relaxation process of full and specific rates - of transition from intermediate state into ''non-reversible'', of desorption into the gas phase and accumUlation of the particles in the intermediate state are obtained
Online Manifold Regularization by Dual Ascending Procedure
Sun, Boliang; Li, Guohui; Jia, Li; Zhang, Hui
2013-01-01
We propose a novel online manifold regularization framework based on the notion of duality in constrained optimization. The Fenchel conjugate of hinge functions is a key to transfer manifold regularization from offline to online in this paper. Our algorithms are derived by gradient ascent in the dual function. For practical purpose, we propose two buffering strategies and two sparse approximations to reduce the computational complexity. Detailed experiments verify the utility of our approache...
Improvements in GRACE Gravity Fields Using Regularization
Save, H.; Bettadpur, S.; Tapley, B. D.
2008-12-01
The unconstrained global gravity field models derived from GRACE are susceptible to systematic errors that show up as broad "stripes" aligned in a North-South direction on the global maps of mass flux. These errors are believed to be a consequence of both systematic and random errors in the data that are amplified by the nature of the gravity field inverse problem. These errors impede scientific exploitation of the GRACE data products, and limit the realizable spatial resolution of the GRACE global gravity fields in certain regions. We use regularization techniques to reduce these "stripe" errors in the gravity field products. The regularization criteria are designed such that there is no attenuation of the signal and that the solutions fit the observations as well as an unconstrained solution. We have used a computationally inexpensive method, normally referred to as "L-ribbon", to find the regularization parameter. This paper discusses the characteristics and statistics of a 5-year time-series of regularized gravity field solutions. The solutions show markedly reduced stripes, are of uniformly good quality over time, and leave little or no systematic observation residuals, which is a frequent consequence of signal suppression from regularization. Up to degree 14, the signal in regularized solution shows correlation greater than 0.8 with the un-regularized CSR Release-04 solutions. Signals from large-amplitude and small-spatial extent events - such as the Great Sumatra Andaman Earthquake of 2004 - are visible in the global solutions without using special post-facto error reduction techniques employed previously in the literature. Hydrological signals as small as 5 cm water-layer equivalent in the small river basins, like Indus and Nile for example, are clearly evident, in contrast to noisy estimates from RL04. The residual variability over the oceans relative to a seasonal fit is small except at higher latitudes, and is evident without the need for de-striping or
LENUS (Irish Health Repository)
Solomon, K
2011-08-01
A repetitive-extragenic palindromic PCR (rep-PCR) subtyping method (DiversiLab) in conjunction with ribotyping, toxinotyping and antimicrobial-susceptibility testing was used to detect subtypes within Clostridium difficile ribotypes 027 and 078. Clinical isolates of ribotypes 027 (toxinotype III) (n = 30) and 078 (toxinotype V) (n = 23) were provided by health-care facilities across the Republic of Ireland over 2 months in 2006 and 1 month in 2009. Ribotype 027 isolates were significantly more related to each other (9 different subtype profiles) when compared to ribotype 078 isolates (14 different profiles) (P = 0.001; cut-off >90 % similarity). Almost half of ribotype 078 isolates (45.5 %) showed no relationship to each other. The clonality of ribotype 027 isolates suggests effective adaptation to the human niche, whereas the considerable genetic diversity within ribotype 078 isolates suggests that they may have originated from a variety of sources. Subtyping correlated well with antimicrobial susceptibility, in particular clindamycin susceptibility for ribotype 027, but diverse antimicrobial-susceptibility profiles were seen in ribotype 078 isolates, even within a single health-care facility. Between 2006 and 2009, a change in the predominant subtype of ribotype 027 was seen, with the recent clone representing half of all ribotype 027 isolates studied. This strain exhibited 89 % similarity to a rep-PCR profile of the North American NAP-1 strain.
Kaushik, Mahima; Kukreti, Shrikant
2015-01-01
Our previous work on structural polymorphism shown at a single nucleotide polymorphism (SNP) (A → G) site located on HS4 region of locus control region (LCR) of β-globin gene has established a hairpin → duplex equilibrium corresponding to A → B like DNA transition (Kaushik M, Kukreti, R., Grover, D., Brahmachari, S.K. and Kukreti S. Nucleic Acids Res. 2003; Kaushik M, Kukreti S. Nucleic Acids Res. 2006). The G-allele of A → G SNP has been shown to be significantly associated with the occurrence of β-thalassemia. Considering the significance of this 11-nt long quasi-palindromic sequence [5'-TGGGG(G/A)CCCCA; HP(G/A)11] of β-globin gene LCR, we further explored the differential behavior of the same DNA sequence with its RNA counterpart, using various biophysical and biochemical techniques. In contrast to its DNA counterpart exhibiting a A → B structural transition and an equilibrium between duplex and hairpin forms, the studied RNA oligonucleotide sequence [5'-UGGGG(G/A)CCCCA; RHP(G/A)11] existed only in duplex form (A-conformation) and did not form hairpin. The single residue difference from A to G led to the unusual thermal stability of the RNA structure formed by the studied sequence. Since, naturally occurring mutations and various SNP sites may stabilize or destabilize the local DNA/RNA secondary structures, these structural transitions may affect the gene expression by a change in the protein-DNA recognition patterns.
Regular Expression Matching and Operational Semantics
Directory of Open Access Journals (Sweden)
Asiri Rathnayake
2011-08-01
Full Text Available Many programming languages and tools, ranging from grep to the Java String library, contain regular expression matchers. Rather than first translating a regular expression into a deterministic finite automaton, such implementations typically match the regular expression on the fly. Thus they can be seen as virtual machines interpreting the regular expression much as if it were a program with some non-deterministic constructs such as the Kleene star. We formalize this implementation technique for regular expression matching using operational semantics. Specifically, we derive a series of abstract machines, moving from the abstract definition of matching to increasingly realistic machines. First a continuation is added to the operational semantics to describe what remains to be matched after the current expression. Next, we represent the expression as a data structure using pointers, which enables redundant searches to be eliminated via testing for pointer equality. From there, we arrive both at Thompson's lockstep construction and a machine that performs some operations in parallel, suitable for implementation on a large number of cores, such as a GPU. We formalize the parallel machine using process algebra and report some preliminary experiments with an implementation on a graphics processor using CUDA.
Regularities, Natural Patterns and Laws of Nature
Directory of Open Access Journals (Sweden)
Stathis Psillos
2014-02-01
Full Text Available The goal of this paper is to sketch an empiricist metaphysics of laws of nature. The key idea is that there are regularities without regularity-enforcers. Differently put, there are natural laws without law-makers of a distinct metaphysical kind. This sketch will rely on the concept of a natural pattern and more significantly on the existence of a network of natural patterns in nature. The relation between a regularity and a pattern will be analysed in terms of mereology. Here is the road map. In section 2, I will briefly discuss the relation between empiricism and metaphysics, aiming to show that an empiricist metaphysics is possible. In section 3, I will offer arguments against stronger metaphysical views of laws. Then, in section 4 I will motivate nomic objectivism. In section 5, I will address the question ‘what is a regularity?’ and will develop a novel answer to it, based on the notion of a natural pattern. In section 6, I will raise the question: ‘what is a law of nature?’, the answer to which will be: a law of nature is a regularity that is characterised by the unity of a natural pattern.
Fractional Regularization Term for Variational Image Registration
Directory of Open Access Journals (Sweden)
Rafael Verdú-Monedero
2009-01-01
Full Text Available Image registration is a widely used task of image analysis with applications in many fields. Its classical formulation and current improvements are given in the spatial domain. In this paper a regularization term based on fractional order derivatives is formulated. This term is defined and implemented in the frequency domain by translating the energy functional into the frequency domain and obtaining the Euler-Lagrange equations which minimize it. The new regularization term leads to a simple formulation and design, being applicable to higher dimensions by using the corresponding multidimensional Fourier transform. The proposed regularization term allows for a real gradual transition from a diffusion registration to a curvature registration which is best suited to some applications and it is not possible in the spatial domain. Results with 3D actual images show the validity of this approach.
International Nuclear Information System (INIS)
Obregon, Octavio; Quevedo, Hernando; Ryan, Michael P.
2004-01-01
We construct a family of time and angular dependent, regular S-brane solutions which corresponds to a simple analytical continuation of the Zipoy-Voorhees 4-dimensional vacuum spacetime. The solutions are asymptotically flat and turn out to be free of singularities without requiring a twist in space. They can be considered as the simplest non-singular generalization of the singular S0-brane solution. We analyze the properties of a representative of this family of solutions and show that it resembles to some extent the asymptotic properties of the regular Kerr S-brane. The R-symmetry corresponds, however, to the general lorentzian symmetry. Several generalizations of this regular solution are derived which include a charged S-brane and an additional dilatonic field. (author)
Online Manifold Regularization by Dual Ascending Procedure
Directory of Open Access Journals (Sweden)
Boliang Sun
2013-01-01
Full Text Available We propose a novel online manifold regularization framework based on the notion of duality in constrained optimization. The Fenchel conjugate of hinge functions is a key to transfer manifold regularization from offline to online in this paper. Our algorithms are derived by gradient ascent in the dual function. For practical purpose, we propose two buffering strategies and two sparse approximations to reduce the computational complexity. Detailed experiments verify the utility of our approaches. An important conclusion is that our online MR algorithms can handle the settings where the target hypothesis is not fixed but drifts with the sequence of examples. We also recap and draw connections to earlier works. This paper paves a way to the design and analysis of online manifold regularization algorithms.
Regular transport dynamics produce chaotic travel times.
Villalobos, Jorge; Muñoz, Víctor; Rogan, José; Zarama, Roberto; Johnson, Neil F; Toledo, Benjamín; Valdivia, Juan Alejandro
2014-06-01
In the hope of making passenger travel times shorter and more reliable, many cities are introducing dedicated bus lanes (e.g., Bogota, London, Miami). Here we show that chaotic travel times are actually a natural consequence of individual bus function, and hence of public transport systems more generally, i.e., chaotic dynamics emerge even when the route is empty and straight, stops and lights are equidistant and regular, and loading times are negligible. More generally, our findings provide a novel example of chaotic dynamics emerging from a single object following Newton's laws of motion in a regularized one-dimensional system.
Regularity of difference equations on Banach spaces
Agarwal, Ravi P; Lizama, Carlos
2014-01-01
This work introduces readers to the topic of maximal regularity for difference equations. The authors systematically present the method of maximal regularity, outlining basic linear difference equations along with relevant results. They address recent advances in the field, as well as basic semigroup and cosine operator theories in the discrete setting. The authors also identify some open problems that readers may wish to take up for further research. This book is intended for graduate students and researchers in the area of difference equations, particularly those with advance knowledge of and interest in functional analysis.
PET regularization by envelope guided conjugate gradients
International Nuclear Information System (INIS)
Kaufman, L.; Neumaier, A.
1996-01-01
The authors propose a new way to iteratively solve large scale ill-posed problems and in particular the image reconstruction problem in positron emission tomography by exploiting the relation between Tikhonov regularization and multiobjective optimization to obtain iteratively approximations to the Tikhonov L-curve and its corner. Monitoring the change of the approximate L-curves allows us to adjust the regularization parameter adaptively during a preconditioned conjugate gradient iteration, so that the desired solution can be reconstructed with a small number of iterations
Matrix regularization of embedded 4-manifolds
International Nuclear Information System (INIS)
Trzetrzelewski, Maciej
2012-01-01
We consider products of two 2-manifolds such as S 2 ×S 2 , embedded in Euclidean space and show that the corresponding 4-volume preserving diffeomorphism algebra can be approximated by a tensor product SU(N)⊗SU(N) i.e. functions on a manifold are approximated by the Kronecker product of two SU(N) matrices. A regularization of the 4-sphere is also performed by constructing N 2 ×N 2 matrix representations of the 4-algebra (and as a byproduct of the 3-algebra which makes the regularization of S 3 also possible).
On a correspondence between regular and non-regular operator monotone functions
DEFF Research Database (Denmark)
Gibilisco, P.; Hansen, Frank; Isola, T.
2009-01-01
We prove the existence of a bijection between the regular and the non-regular operator monotone functions satisfying a certain functional equation. As an application we give a new proof of the operator monotonicity of certain functions related to the Wigner-Yanase-Dyson skew information....
Regularity and irreversibility of weekly travel behavior
Kitamura, R.; van der Hoorn, A.I.J.M.
1987-01-01
Dynamic characteristics of travel behavior are analyzed in this paper using weekly travel diaries from two waves of panel surveys conducted six months apart. An analysis of activity engagement indicates the presence of significant regularity in weekly activity participation between the two waves.
Regular and context-free nominal traces
DEFF Research Database (Denmark)
Degano, Pierpaolo; Ferrari, Gian-Luigi; Mezzetti, Gianluca
2017-01-01
Two kinds of automata are presented, for recognising new classes of regular and context-free nominal languages. We compare their expressive power with analogous proposals in the literature, showing that they express novel classes of languages. Although many properties of classical languages hold ...
Faster 2-regular information-set decoding
Bernstein, D.J.; Lange, T.; Peters, C.P.; Schwabe, P.; Chee, Y.M.
2011-01-01
Fix positive integers B and w. Let C be a linear code over F 2 of length Bw. The 2-regular-decoding problem is to find a nonzero codeword consisting of w length-B blocks, each of which has Hamming weight 0 or 2. This problem appears in attacks on the FSB (fast syndrome-based) hash function and
Complexity in union-free regular languages
Czech Academy of Sciences Publication Activity Database
Jirásková, G.; Masopust, Tomáš
2011-01-01
Roč. 22, č. 7 (2011), s. 1639-1653 ISSN 0129-0541 Institutional research plan: CEZ:AV0Z10190503 Keywords : Union-free regular language * one-cycle-free-path automaton * descriptional complexity Subject RIV: BA - General Mathematics Impact factor: 0.379, year: 2011 http://www.worldscinet.com/ijfcs/22/2207/S0129054111008933.html
Regular Gleason Measures and Generalized Effect Algebras
Dvurečenskij, Anatolij; Janda, Jiří
2015-12-01
We study measures, finitely additive measures, regular measures, and σ-additive measures that can attain even infinite values on the quantum logic of a Hilbert space. We show when particular classes of non-negative measures can be studied in the frame of generalized effect algebras.
Regularization of finite temperature string theories
International Nuclear Information System (INIS)
Leblanc, Y.; Knecht, M.; Wallet, J.C.
1990-01-01
The tachyonic divergences occurring in the free energy of various string theories at finite temperature are eliminated through the use of regularization schemes and analytic continuations. For closed strings, we obtain finite expressions which, however, develop an imaginary part above the Hagedorn temperature, whereas open string theories are still plagued with dilatonic divergences. (orig.)
A Sim(2 invariant dimensional regularization
Directory of Open Access Journals (Sweden)
J. Alfaro
2017-09-01
Full Text Available We introduce a Sim(2 invariant dimensional regularization of loop integrals. Then we can compute the one loop quantum corrections to the photon self energy, electron self energy and vertex in the Electrodynamics sector of the Very Special Relativity Standard Model (VSRSM.
Continuum regularized Yang-Mills theory
International Nuclear Information System (INIS)
Sadun, L.A.
1987-01-01
Using the machinery of stochastic quantization, Z. Bern, M. B. Halpern, C. Taubes and I recently proposed a continuum regularization technique for quantum field theory. This regularization may be implemented by applying a regulator to either the (d + 1)-dimensional Parisi-Wu Langevin equation or, equivalently, to the d-dimensional second order Schwinger-Dyson (SD) equations. This technique is non-perturbative, respects all gauge and Lorentz symmetries, and is consistent with a ghost-free gauge fixing (Zwanziger's). This thesis is a detailed study of this regulator, and of regularized Yang-Mills theory, using both perturbative and non-perturbative techniques. The perturbative analysis comes first. The mechanism of stochastic quantization is reviewed, and a perturbative expansion based on second-order SD equations is developed. A diagrammatic method (SD diagrams) for evaluating terms of this expansion is developed. We apply the continuum regulator to a scalar field theory. Using SD diagrams, we show that all Green functions can be rendered finite to all orders in perturbation theory. Even non-renormalizable theories can be regularized. The continuum regulator is then applied to Yang-Mills theory, in conjunction with Zwanziger's gauge fixing. A perturbative expansion of the regulator is incorporated into the diagrammatic method. It is hoped that the techniques discussed in this thesis will contribute to the construction of a renormalized Yang-Mills theory is 3 and 4 dimensions
Gravitational lensing by a regular black hole
International Nuclear Information System (INIS)
Eiroa, Ernesto F; Sendra, Carlos M
2011-01-01
In this paper, we study a regular Bardeen black hole as a gravitational lens. We find the strong deflection limit for the deflection angle, from which we obtain the positions and magnifications of the relativistic images. As an example, we apply the results to the particular case of the supermassive black hole at the center of our galaxy.
Gravitational lensing by a regular black hole
Energy Technology Data Exchange (ETDEWEB)
Eiroa, Ernesto F; Sendra, Carlos M, E-mail: eiroa@iafe.uba.ar, E-mail: cmsendra@iafe.uba.ar [Instituto de Astronomia y Fisica del Espacio, CC 67, Suc. 28, 1428, Buenos Aires (Argentina)
2011-04-21
In this paper, we study a regular Bardeen black hole as a gravitational lens. We find the strong deflection limit for the deflection angle, from which we obtain the positions and magnifications of the relativistic images. As an example, we apply the results to the particular case of the supermassive black hole at the center of our galaxy.
Analytic stochastic regularization and gange invariance
International Nuclear Information System (INIS)
Abdalla, E.; Gomes, M.; Lima-Santos, A.
1986-05-01
A proof that analytic stochastic regularization breaks gauge invariance is presented. This is done by an explicit one loop calculation of the vaccum polarization tensor in scalar electrodynamics, which turns out not to be transversal. The counterterm structure, Langevin equations and the construction of composite operators in the general framework of stochastic quantization, are also analysed. (Author) [pt
Annotation of regular polysemy and underspecification
DEFF Research Database (Denmark)
Martínez Alonso, Héctor; Pedersen, Bolette Sandford; Bel, Núria
2013-01-01
We present the result of an annotation task on regular polysemy for a series of seman- tic classes or dot types in English, Dan- ish and Spanish. This article describes the annotation process, the results in terms of inter-encoder agreement, and the sense distributions obtained with two methods...
Stabilization, pole placement, and regular implementability
Belur, MN; Trentelman, HL
In this paper, we study control by interconnection of linear differential systems. We give necessary and sufficient conditions for regular implementability of a-given linear, differential system. We formulate the problems of stabilization and pole placement as problems of finding a suitable,
12 CFR 725.3 - Regular membership.
2010-01-01
... UNION ADMINISTRATION CENTRAL LIQUIDITY FACILITY § 725.3 Regular membership. (a) A natural person credit....5(b) of this part, and forwarding with its completed application funds equal to one-half of this... 1, 1979, is not required to forward these funds to the Facility until October 1, 1979. (3...
Supervised scale-regularized linear convolutionary filters
DEFF Research Database (Denmark)
Loog, Marco; Lauze, Francois Bernard
2017-01-01
also be solved relatively efficient. All in all, the idea is to properly control the scale of a trained filter, which we solve by introducing a specific regularization term into the overall objective function. We demonstrate, on an artificial filter learning problem, the capabil- ities of our basic...
On regular riesz operators | Raubenheimer | Quaestiones ...
African Journals Online (AJOL)
The r-asymptotically quasi finite rank operators on Banach lattices are examples of regular Riesz operators. We characterise Riesz elements in a subalgebra of a Banach algebra in terms of Riesz elements in the Banach algebra. This enables us to characterise r-asymptotically quasi finite rank operators in terms of adjoint ...
Regularized Discriminant Analysis: A Large Dimensional Study
Yang, Xiaoke
2018-04-28
In this thesis, we focus on studying the performance of general regularized discriminant analysis (RDA) classifiers. The data used for analysis is assumed to follow Gaussian mixture model with different means and covariances. RDA offers a rich class of regularization options, covering as special cases the regularized linear discriminant analysis (RLDA) and the regularized quadratic discriminant analysis (RQDA) classi ers. We analyze RDA under the double asymptotic regime where the data dimension and the training size both increase in a proportional way. This double asymptotic regime allows for application of fundamental results from random matrix theory. Under the double asymptotic regime and some mild assumptions, we show that the asymptotic classification error converges to a deterministic quantity that only depends on the data statistical parameters and dimensions. This result not only implicates some mathematical relations between the misclassification error and the class statistics, but also can be leveraged to select the optimal parameters that minimize the classification error, thus yielding the optimal classifier. Validation results on the synthetic data show a good accuracy of our theoretical findings. We also construct a general consistent estimator to approximate the true classification error in consideration of the unknown previous statistics. We benchmark the performance of our proposed consistent estimator against classical estimator on synthetic data. The observations demonstrate that the general estimator outperforms others in terms of mean squared error (MSE).
Complexity in union-free regular languages
Czech Academy of Sciences Publication Activity Database
Jirásková, G.; Masopust, Tomáš
2011-01-01
Roč. 22, č. 7 (2011), s. 1639-1653 ISSN 0129-0541 Institutional research plan: CEZ:AV0Z10190503 Keywords : Union-free regular language * one-cycle-free- path automaton * descriptional complexity Subject RIV: BA - General Mathematics Impact factor: 0.379, year: 2011 http://www.worldscinet.com/ijfcs/22/2207/S0129054111008933.html
Bit-coded regular expression parsing
DEFF Research Database (Denmark)
Nielsen, Lasse; Henglein, Fritz
2011-01-01
the DFA-based parsing algorithm due to Dub ´e and Feeley to emit the bits of the bit representation without explicitly materializing the parse tree itself. We furthermore show that Frisch and Cardelli’s greedy regular expression parsing algorithm can be straightforwardly modified to produce bit codings...
Tetravalent one-regular graphs of order 4p2
DEFF Research Database (Denmark)
Feng, Yan-Quan; Kutnar, Klavdija; Marusic, Dragan
2014-01-01
A graph is one-regular if its automorphism group acts regularly on the set of its arcs. In this paper tetravalent one-regular graphs of order 4p2, where p is a prime, are classified.......A graph is one-regular if its automorphism group acts regularly on the set of its arcs. In this paper tetravalent one-regular graphs of order 4p2, where p is a prime, are classified....
Baburajendran, Nithya; Palasingam, Paaventhan; Ng, Calista Keow Leng; Jauch, Ralf; Kolatkar, Prasanna R.
2009-01-01
The bone morphogenetic protein (BMP) signalling pathway regulates diverse processes such as cell differentiation, anterior/posterior axis specification, cell growth and the formation of extra-embryonic tissues. The transcription factor Smad1 relays the BMP signal from the cytoplasm to the nucleus, where it binds short DNA-sequence motifs and regulates gene expression. However, how Smad1 selectively targets particular genomic regions is poorly understood. In order to understand the physical basis of the specific interaction of Smad1 with DNA and to contrast it with the highly homologous but functionally distinct Smad3 protein, the DNA-binding Mad-homology 1 (MH1) domain of Smad1 was cocrystallized with a 17-mer palindromic Smad-binding element (SBE). The extensive optimizations of the length, binding-site spacing and terminal sequences of the DNA element in combination with the other crystallization parameters necessary for obtaining diffraction-quality crystals are described here. A 2.7 Å resolution native data set was collected at the National Synchrotron Radiation Research Centre, Taiwan, from crystals grown in a solution containing 0.2 M ammonium tartrate dibasic, 20% PEG 3350, 3% 2-propanol and 10% glycerol. The data set was indexed and merged in space group P222, with unit-cell parameters a = 73.94, b = 77.49, c = 83.78 Å, α = β = γ = 90°. The solvent content in the unit cell is consistent with the presence of two Smad1 MH1 molecules bound to the duplex DNA in the asymmetric unit. PMID:19923727
Save, H.; Bettadpur, S. V.
2013-12-01
It has been demonstrated before that using Tikhonov regularization produces spherical harmonic solutions from GRACE that have very little residual stripes while capturing all the signal observed by GRACE within the noise level. This paper demonstrates a two-step process and uses Tikhonov regularization to remove the residual stripes in the CSR regularized spherical harmonic coefficients when computing the spatial projections. We discuss methods to produce mass anomaly grids that have no stripe features while satisfying the necessary condition of capturing all observed signal within the GRACE noise level.
Extreme values, regular variation and point processes
Resnick, Sidney I
1987-01-01
Extremes Values, Regular Variation and Point Processes is a readable and efficient account of the fundamental mathematical and stochastic process techniques needed to study the behavior of extreme values of phenomena based on independent and identically distributed random variables and vectors It presents a coherent treatment of the distributional and sample path fundamental properties of extremes and records It emphasizes the core primacy of three topics necessary for understanding extremes the analytical theory of regularly varying functions; the probabilistic theory of point processes and random measures; and the link to asymptotic distribution approximations provided by the theory of weak convergence of probability measures in metric spaces The book is self-contained and requires an introductory measure-theoretic course in probability as a prerequisite Almost all sections have an extensive list of exercises which extend developments in the text, offer alternate approaches, test mastery and provide for enj...
Stream Processing Using Grammars and Regular Expressions
DEFF Research Database (Denmark)
Rasmussen, Ulrik Terp
disambiguation. The first algorithm operates in two passes in a semi-streaming fashion, using a constant amount of working memory and an auxiliary tape storage which is written in the first pass and consumed by the second. The second algorithm is a single-pass and optimally streaming algorithm which outputs...... as much of the parse tree as is semantically possible based on the input prefix read so far, and resorts to buffering as many symbols as is required to resolve the next choice. Optimality is obtained by performing a PSPACE-complete pre-analysis on the regular expression. In the second part we present...... Kleenex, a language for expressing high-performance streaming string processing programs as regular grammars with embedded semantic actions, and its compilation to streaming string transducers with worst-case linear-time performance. Its underlying theory is based on transducer decomposition into oracle...
Describing chaotic attractors: Regular and perpetual points
Dudkowski, Dawid; Prasad, Awadhesh; Kapitaniak, Tomasz
2018-03-01
We study the concepts of regular and perpetual points for describing the behavior of chaotic attractors in dynamical systems. The idea of these points, which have been recently introduced to theoretical investigations, is thoroughly discussed and extended into new types of models. We analyze the correlation between regular and perpetual points, as well as their relation with phase space, showing the potential usefulness of both types of points in the qualitative description of co-existing states. The ability of perpetual points in finding attractors is indicated, along with its potential cause. The location of chaotic trajectories and sets of considered points is investigated and the study on the stability of systems is shown. The statistical analysis of the observing desired states is performed. We focus on various types of dynamical systems, i.e., chaotic flows with self-excited and hidden attractors, forced mechanical models, and semiconductor superlattices, exhibiting the universality of appearance of the observed patterns and relations.
Chaos regularization of quantum tunneling rates
International Nuclear Information System (INIS)
Pecora, Louis M.; Wu Dongho; Lee, Hoshik; Antonsen, Thomas; Lee, Ming-Jer; Ott, Edward
2011-01-01
Quantum tunneling rates through a barrier separating two-dimensional, symmetric, double-well potentials are shown to depend on the classical dynamics of the billiard trajectories in each well and, hence, on the shape of the wells. For shapes that lead to regular (integrable) classical dynamics the tunneling rates fluctuate greatly with eigenenergies of the states sometimes by over two orders of magnitude. Contrarily, shapes that lead to completely chaotic trajectories lead to tunneling rates whose fluctuations are greatly reduced, a phenomenon we call regularization of tunneling rates. We show that a random-plane-wave theory of tunneling accounts for the mean tunneling rates and the small fluctuation variances for the chaotic systems.
Least square regularized regression in sum space.
Xu, Yong-Li; Chen, Di-Rong; Li, Han-Xiong; Liu, Lu
2013-04-01
This paper proposes a least square regularized regression algorithm in sum space of reproducing kernel Hilbert spaces (RKHSs) for nonflat function approximation, and obtains the solution of the algorithm by solving a system of linear equations. This algorithm can approximate the low- and high-frequency component of the target function with large and small scale kernels, respectively. The convergence and learning rate are analyzed. We measure the complexity of the sum space by its covering number and demonstrate that the covering number can be bounded by the product of the covering numbers of basic RKHSs. For sum space of RKHSs with Gaussian kernels, by choosing appropriate parameters, we tradeoff the sample error and regularization error, and obtain a polynomial learning rate, which is better than that in any single RKHS. The utility of this method is illustrated with two simulated data sets and five real-life databases.
Contour Propagation With Riemannian Elasticity Regularization
DEFF Research Database (Denmark)
Bjerre, Troels; Hansen, Mads Fogtmann; Sapru, W.
2011-01-01
Purpose/Objective(s): Adaptive techniques allow for correction of spatial changes during the time course of the fractionated radiotherapy. Spatial changes include tumor shrinkage and weight loss, causing tissue deformation and residual positional errors even after translational and rotational image...... the planning CT onto the rescans and correcting to reflect actual anatomical changes. For deformable registration, a free-form, multi-level, B-spline deformation model with Riemannian elasticity, penalizing non-rigid local deformations, and volumetric changes, was used. Regularization parameters was defined...... on the original delineation and tissue deformation in the time course between scans form a better starting point than rigid propagation. There was no significant difference of locally and globally defined regularization. The method used in the present study suggests that deformed contours need to be reviewed...
Thin accretion disk around regular black hole
Directory of Open Access Journals (Sweden)
QIU Tianqi
2014-08-01
Full Text Available The Penrose′s cosmic censorship conjecture says that naked singularities do not exist in nature.So,it seems reasonable to further conjecture that not even a singularity exists in nature.In this paper,a regular black hole without singularity is studied in detail,especially on its thin accretion disk,energy flux,radiation temperature and accretion efficiency.It is found that the interaction of regular black hole is stronger than that of the Schwarzschild black hole. Furthermore,the thin accretion will be more efficiency to lost energy while the mass of black hole decreased. These particular properties may be used to distinguish between black holes.
Convex nonnegative matrix factorization with manifold regularization.
Hu, Wenjun; Choi, Kup-Sze; Wang, Peiliang; Jiang, Yunliang; Wang, Shitong
2015-03-01
Nonnegative Matrix Factorization (NMF) has been extensively applied in many areas, including computer vision, pattern recognition, text mining, and signal processing. However, nonnegative entries are usually required for the data matrix in NMF, which limits its application. Besides, while the basis and encoding vectors obtained by NMF can represent the original data in low dimension, the representations do not always reflect the intrinsic geometric structure embedded in the data. Motivated by manifold learning and Convex NMF (CNMF), we propose a novel matrix factorization method called Graph Regularized and Convex Nonnegative Matrix Factorization (GCNMF) by introducing a graph regularized term into CNMF. The proposed matrix factorization technique not only inherits the intrinsic low-dimensional manifold structure, but also allows the processing of mixed-sign data matrix. Clustering experiments on nonnegative and mixed-sign real-world data sets are conducted to demonstrate the effectiveness of the proposed method. Copyright © 2014 Elsevier Ltd. All rights reserved.
A short proof of increased parabolic regularity
Directory of Open Access Journals (Sweden)
Stephen Pankavich
2015-08-01
Full Text Available We present a short proof of the increased regularity obtained by solutions to uniformly parabolic partial differential equations. Though this setting is fairly introductory, our new method of proof, which uses a priori estimates and an inductive method, can be extended to prove analogous results for problems with time-dependent coefficients, advection-diffusion or reaction diffusion equations, and nonlinear PDEs even when other tools, such as semigroup methods or the use of explicit fundamental solutions, are unavailable.
Regular black hole in three dimensions
Myung, Yun Soo; Yoon, Myungseok
2008-01-01
We find a new black hole in three dimensional anti-de Sitter space by introducing an anisotropic perfect fluid inspired by the noncommutative black hole. This is a regular black hole with two horizons. We compare thermodynamics of this black hole with that of non-rotating BTZ black hole. The first-law of thermodynamics is not compatible with the Bekenstein-Hawking entropy.
Sparse regularization for force identification using dictionaries
Qiao, Baijie; Zhang, Xingwu; Wang, Chenxi; Zhang, Hang; Chen, Xuefeng
2016-04-01
The classical function expansion method based on minimizing l2-norm of the response residual employs various basis functions to represent the unknown force. Its difficulty lies in determining the optimum number of basis functions. Considering the sparsity of force in the time domain or in other basis space, we develop a general sparse regularization method based on minimizing l1-norm of the coefficient vector of basis functions. The number of basis functions is adaptively determined by minimizing the number of nonzero components in the coefficient vector during the sparse regularization process. First, according to the profile of the unknown force, the dictionary composed of basis functions is determined. Second, a sparsity convex optimization model for force identification is constructed. Third, given the transfer function and the operational response, Sparse reconstruction by separable approximation (SpaRSA) is developed to solve the sparse regularization problem of force identification. Finally, experiments including identification of impact and harmonic forces are conducted on a cantilever thin plate structure to illustrate the effectiveness and applicability of SpaRSA. Besides the Dirac dictionary, other three sparse dictionaries including Db6 wavelets, Sym4 wavelets and cubic B-spline functions can also accurately identify both the single and double impact forces from highly noisy responses in a sparse representation frame. The discrete cosine functions can also successfully reconstruct the harmonic forces including the sinusoidal, square and triangular forces. Conversely, the traditional Tikhonov regularization method with the L-curve criterion fails to identify both the impact and harmonic forces in these cases.
Analytic stochastic regularization and gauge theories
International Nuclear Information System (INIS)
Abdalla, E.; Gomes, M.; Lima-Santos, A.
1987-04-01
We prove that analytic stochatic regularization braks gauge invariance. This is done by an explicit one loop calculation of the two three and four point vertex functions of the gluon field in scalar chromodynamics, which turns out not to be geuge invariant. We analyse the counter term structure, Langevin equations and the construction of composite operators in the general framework of stochastic quantization. (author) [pt
Preconditioners for regularized saddle point matrices
Czech Academy of Sciences Publication Activity Database
Axelsson, Owe
2011-01-01
Roč. 19, č. 2 (2011), s. 91-112 ISSN 1570-2820 Institutional research plan: CEZ:AV0Z30860518 Keywords : saddle point matrices * preconditioning * regularization * eigenvalue clustering Subject RIV: BA - General Mathematics Impact factor: 0.533, year: 2011 http://www.degruyter.com/view/j/jnma.2011.19.issue-2/jnum.2011.005/jnum.2011.005. xml
Analytic stochastic regularization: gauge and supersymmetry theories
International Nuclear Information System (INIS)
Abdalla, M.C.B.
1988-01-01
Analytic stochastic regularization for gauge and supersymmetric theories is considered. Gauge invariance in spinor and scalar QCD is verified to brak fown by an explicit one loop computation of the two, theree and four point vertex function of the gluon field. As a result, non gauge invariant counterterms must be added. However, in the supersymmetric multiplets there is a cancellation rendering the counterterms gauge invariant. The calculation is considered at one loop order. (author) [pt
Regularized forecasting of chaotic dynamical systems
International Nuclear Information System (INIS)
Bollt, Erik M.
2017-01-01
While local models of dynamical systems have been highly successful in terms of using extensive data sets observing even a chaotic dynamical system to produce useful forecasts, there is a typical problem as follows. Specifically, with k-near neighbors, kNN method, local observations occur due to recurrences in a chaotic system, and this allows for local models to be built by regression to low dimensional polynomial approximations of the underlying system estimating a Taylor series. This has been a popular approach, particularly in context of scalar data observations which have been represented by time-delay embedding methods. However such local models can generally allow for spatial discontinuities of forecasts when considered globally, meaning jumps in predictions because the collected near neighbors vary from point to point. The source of these discontinuities is generally that the set of near neighbors varies discontinuously with respect to the position of the sample point, and so therefore does the model built from the near neighbors. It is possible to utilize local information inferred from near neighbors as usual but at the same time to impose a degree of regularity on a global scale. We present here a new global perspective extending the general local modeling concept. In so doing, then we proceed to show how this perspective allows us to impose prior presumed regularity into the model, by involving the Tikhonov regularity theory, since this classic perspective of optimization in ill-posed problems naturally balances fitting an objective with some prior assumed form of the result, such as continuity or derivative regularity for example. This all reduces to matrix manipulations which we demonstrate on a simple data set, with the implication that it may find much broader context.
Minimal length uncertainty relation and ultraviolet regularization
Kempf, Achim; Mangano, Gianpiero
1997-06-01
Studies in string theory and quantum gravity suggest the existence of a finite lower limit Δx0 to the possible resolution of distances, at the latest on the scale of the Planck length of 10-35 m. Within the framework of the Euclidean path integral we explicitly show ultraviolet regularization in field theory through this short distance structure. Both rotation and translation invariance can be preserved. An example is studied in detail.
Regularity and chaos in cavity QED
International Nuclear Information System (INIS)
Bastarrachea-Magnani, Miguel Angel; López-del-Carpio, Baldemar; Chávez-Carlos, Jorge; Lerma-Hernández, Sergio; Hirsch, Jorge G
2017-01-01
The interaction of a quantized electromagnetic field in a cavity with a set of two-level atoms inside it can be described with algebraic Hamiltonians of increasing complexity, from the Rabi to the Dicke models. Their algebraic character allows, through the use of coherent states, a semiclassical description in phase space, where the non-integrable Dicke model has regions associated with regular and chaotic motion. The appearance of classical chaos can be quantified calculating the largest Lyapunov exponent over the whole available phase space for a given energy. In the quantum regime, employing efficient diagonalization techniques, we are able to perform a detailed quantitative study of the regular and chaotic regions, where the quantum participation ratio (P R ) of coherent states on the eigenenergy basis plays a role equivalent to the Lyapunov exponent. It is noted that, in the thermodynamic limit, dividing the participation ratio by the number of atoms leads to a positive value in chaotic regions, while it tends to zero in the regular ones. (paper)
Solution path for manifold regularized semisupervised classification.
Wang, Gang; Wang, Fei; Chen, Tao; Yeung, Dit-Yan; Lochovsky, Frederick H
2012-04-01
Traditional learning algorithms use only labeled data for training. However, labeled examples are often difficult or time consuming to obtain since they require substantial human labeling efforts. On the other hand, unlabeled data are often relatively easy to collect. Semisupervised learning addresses this problem by using large quantities of unlabeled data with labeled data to build better learning algorithms. In this paper, we use the manifold regularization approach to formulate the semisupervised learning problem where a regularization framework which balances a tradeoff between loss and penalty is established. We investigate different implementations of the loss function and identify the methods which have the least computational expense. The regularization hyperparameter, which determines the balance between loss and penalty, is crucial to model selection. Accordingly, we derive an algorithm that can fit the entire path of solutions for every value of the hyperparameter. Its computational complexity after preprocessing is quadratic only in the number of labeled examples rather than the total number of labeled and unlabeled examples.
Regularizations: different recipes for identical situations
International Nuclear Information System (INIS)
Gambin, E.; Lobo, C.O.; Battistel, O.A.
2004-03-01
We present a discussion where the choice of the regularization procedure and the routing for the internal lines momenta are put at the same level of arbitrariness in the analysis of Ward identities involving simple and well-known problems in QFT. They are the complex self-interacting scalar field and two simple models where the SVV and AVV process are pertinent. We show that, in all these problems, the conditions to symmetry relations preservation are put in terms of the same combination of divergent Feynman integrals, which are evaluated in the context of a very general calculational strategy, concerning the manipulations and calculations involving divergences. Within the adopted strategy, all the arbitrariness intrinsic to the problem are still maintained in the final results and, consequently, a perfect map can be obtained with the corresponding results of the traditional regularization techniques. We show that, when we require an universal interpretation for the arbitrariness involved, in order to get consistency with all stated physical constraints, a strong condition is imposed for regularizations which automatically eliminates the ambiguities associated to the routing of the internal lines momenta of loops. The conclusion is clean and sound: the association between ambiguities and unavoidable symmetry violations in Ward identities cannot be maintained if an unique recipe is required for identical situations in the evaluation of divergent physical amplitudes. (author)
Parekh, Ankit
Sparsity has become the basis of some important signal processing methods over the last ten years. Many signal processing problems (e.g., denoising, deconvolution, non-linear component analysis) can be expressed as inverse problems. Sparsity is invoked through the formulation of an inverse problem with suitably designed regularization terms. The regularization terms alone encode sparsity into the problem formulation. Often, the ℓ1 norm is used to induce sparsity, so much so that ℓ1 regularization is considered to be `modern least-squares'. The use of ℓ1 norm, as a sparsity-inducing regularizer, leads to a convex optimization problem, which has several benefits: the absence of extraneous local minima, well developed theory of globally convergent algorithms, even for large-scale problems. Convex regularization via the ℓ1 norm, however, tends to under-estimate the non-zero values of sparse signals. In order to estimate the non-zero values more accurately, non-convex regularization is often favored over convex regularization. However, non-convex regularization generally leads to non-convex optimization, which suffers from numerous issues: convergence may be guaranteed to only a stationary point, problem specific parameters may be difficult to set, and the solution is sensitive to the initialization of the algorithm. The first part of this thesis is aimed toward combining the benefits of non-convex regularization and convex optimization to estimate sparse signals more effectively. To this end, we propose to use parameterized non-convex regularizers with designated non-convexity and provide a range for the non-convex parameter so as to ensure that the objective function is strictly convex. By ensuring convexity of the objective function (sum of data-fidelity and non-convex regularizer), we can make use of a wide variety of convex optimization algorithms to obtain the unique global minimum reliably. The second part of this thesis proposes a non-linear signal
Sparsity regularization for parameter identification problems
International Nuclear Information System (INIS)
Jin, Bangti; Maass, Peter
2012-01-01
The investigation of regularization schemes with sparsity promoting penalty terms has been one of the dominant topics in the field of inverse problems over the last years, and Tikhonov functionals with ℓ p -penalty terms for 1 ⩽ p ⩽ 2 have been studied extensively. The first investigations focused on regularization properties of the minimizers of such functionals with linear operators and on iteration schemes for approximating the minimizers. These results were quickly transferred to nonlinear operator equations, including nonsmooth operators and more general function space settings. The latest results on regularization properties additionally assume a sparse representation of the true solution as well as generalized source conditions, which yield some surprising and optimal convergence rates. The regularization theory with ℓ p sparsity constraints is relatively complete in this setting; see the first part of this review. In contrast, the development of efficient numerical schemes for approximating minimizers of Tikhonov functionals with sparsity constraints for nonlinear operators is still ongoing. The basic iterated soft shrinkage approach has been extended in several directions and semi-smooth Newton methods are becoming applicable in this field. In particular, the extension to more general non-convex, non-differentiable functionals by variational principles leads to a variety of generalized iteration schemes. We focus on such iteration schemes in the second part of this review. A major part of this survey is devoted to applying sparsity constrained regularization techniques to parameter identification problems for partial differential equations, which we regard as the prototypical setting for nonlinear inverse problems. Parameter identification problems exhibit different levels of complexity and we aim at characterizing a hierarchy of such problems. The operator defining these inverse problems is the parameter-to-state mapping. We first summarize some
Learning Sparse Visual Representations with Leaky Capped Norm Regularizers
Wangni, Jianqiao; Lin, Dahua
2017-01-01
Sparsity inducing regularization is an important part for learning over-complete visual representations. Despite the popularity of $\\ell_1$ regularization, in this paper, we investigate the usage of non-convex regularizations in this problem. Our contribution consists of three parts. First, we propose the leaky capped norm regularization (LCNR), which allows model weights below a certain threshold to be regularized more strongly as opposed to those above, therefore imposes strong sparsity and...
Temporal regularity of the environment drives time perception
van Rijn, H; Rhodes, D; Di Luca, M
2016-01-01
It’s reasonable to assume that a regularly paced sequence should be perceived as regular, but here we show that perceived regularity depends on the context in which the sequence is embedded. We presented one group of participants with perceptually regularly paced sequences, and another group of participants with mostly irregularly paced sequences (75% irregular, 25% regular). The timing of the final stimulus in each sequence could be var- ied. In one experiment, we asked whether the last stim...
Directory of Open Access Journals (Sweden)
Dustin Kai Yan Lau
2014-03-01
Full Text Available Background Unlike alphabetic languages, Chinese uses a logographic script. However, the pronunciation of many character’s phonetic radical has the same pronunciation as the character as a whole. These are considered regular characters and can be read through a lexical non-semantic route (Weekes & Chen, 1999. Pseudocharacters are another way to study this non-semantic route. A pseudocharacter is the combination of existing semantic and phonetic radicals in their legal positions resulting in a non-existing character (Ho, Chan, Chung, Lee, & Tsang, 2007. Pseudocharacters can be pronounced by direct derivation from the sound of its phonetic radical. Conversely, if the pronunciation of a character does not follow that of the phonetic radical, it is considered as irregular and can only be correctly read through the lexical-semantic route. The aim of the current investigation was to examine reading aloud in normal adults. We hypothesized that the regularity effect, previously described for alphabetical scripts and acquired dyslexic patients of Chinese (Weekes & Chen, 1999; Wu, Liu, Sun, Chromik, & Zhang, 2014, would also be present in normal adult Chinese readers. Method Participants. Thirty (50% female native Hong Kong Cantonese speakers with a mean age of 19.6 years and a mean education of 12.9 years. Stimuli. Sixty regular-, 60 irregular-, and 60 pseudo-characters (with at least 75% of name agreement in Chinese were matched by initial phoneme, number of strokes and family size. Additionally, regular- and irregular-characters were matched by frequency (low and consistency. Procedure. Each participant was asked to read aloud the stimuli presented on a laptop using the DMDX software. The order of stimuli presentation was randomized. Data analysis. ANOVAs were carried out by participants and items with RTs and errors as dependent variables and type of stimuli (regular-, irregular- and pseudo-character as repeated measures (F1 or between subject
Convergence and fluctuations of Regularized Tyler estimators
Kammoun, Abla; Couillet, Romain; Pascal, Frederic; Alouini, Mohamed-Slim
2015-01-01
This article studies the behavior of regularized Tyler estimators (RTEs) of scatter matrices. The key advantages of these estimators are twofold. First, they guarantee by construction a good conditioning of the estimate and second, being a derivative of robust Tyler estimators, they inherit their robustness properties, notably their resilience to the presence of outliers. Nevertheless, one major problem that poses the use of RTEs in practice is represented by the question of setting the regularization parameter p. While a high value of p is likely to push all the eigenvalues away from zero, it comes at the cost of a larger bias with respect to the population covariance matrix. A deep understanding of the statistics of RTEs is essential to come up with appropriate choices for the regularization parameter. This is not an easy task and might be out of reach, unless one considers asymptotic regimes wherein the number of observations n and/or their size N increase together. First asymptotic results have recently been obtained under the assumption that N and n are large and commensurable. Interestingly, no results concerning the regime of n going to infinity with N fixed exist, even though the investigation of this assumption has usually predated the analysis of the most difficult N and n large case. This motivates our work. In particular, we prove in the present paper that the RTEs converge to a deterministic matrix when n → ∞ with N fixed, which is expressed as a function of the theoretical covariance matrix. We also derive the fluctuations of the RTEs around this deterministic matrix and establish that these fluctuations converge in distribution to a multivariate Gaussian distribution with zero mean and a covariance depending on the population covariance and the parameter.
Convergence and fluctuations of Regularized Tyler estimators
Kammoun, Abla
2015-10-26
This article studies the behavior of regularized Tyler estimators (RTEs) of scatter matrices. The key advantages of these estimators are twofold. First, they guarantee by construction a good conditioning of the estimate and second, being a derivative of robust Tyler estimators, they inherit their robustness properties, notably their resilience to the presence of outliers. Nevertheless, one major problem that poses the use of RTEs in practice is represented by the question of setting the regularization parameter p. While a high value of p is likely to push all the eigenvalues away from zero, it comes at the cost of a larger bias with respect to the population covariance matrix. A deep understanding of the statistics of RTEs is essential to come up with appropriate choices for the regularization parameter. This is not an easy task and might be out of reach, unless one considers asymptotic regimes wherein the number of observations n and/or their size N increase together. First asymptotic results have recently been obtained under the assumption that N and n are large and commensurable. Interestingly, no results concerning the regime of n going to infinity with N fixed exist, even though the investigation of this assumption has usually predated the analysis of the most difficult N and n large case. This motivates our work. In particular, we prove in the present paper that the RTEs converge to a deterministic matrix when n → ∞ with N fixed, which is expressed as a function of the theoretical covariance matrix. We also derive the fluctuations of the RTEs around this deterministic matrix and establish that these fluctuations converge in distribution to a multivariate Gaussian distribution with zero mean and a covariance depending on the population covariance and the parameter.
The use of regularization in inferential measurements
International Nuclear Information System (INIS)
Hines, J. Wesley; Gribok, Andrei V.; Attieh, Ibrahim; Uhrig, Robert E.
1999-01-01
Inferential sensing is the prediction of a plant variable through the use of correlated plant variables. A correct prediction of the variable can be used to monitor sensors for drift or other failures making periodic instrument calibrations unnecessary. This move from periodic to condition based maintenance can reduce costs and increase the reliability of the instrument. Having accurate, reliable measurements is important for signals that may impact safety or profitability. This paper investigates how collinearity adversely affects inferential sensing by making the results inconsistent and unrepeatable; and presents regularization as a potential solution (author) (ml)
Regularization ambiguities in loop quantum gravity
International Nuclear Information System (INIS)
Perez, Alejandro
2006-01-01
One of the main achievements of loop quantum gravity is the consistent quantization of the analog of the Wheeler-DeWitt equation which is free of ultraviolet divergences. However, ambiguities associated to the intermediate regularization procedure lead to an apparently infinite set of possible theories. The absence of an UV problem--the existence of well-behaved regularization of the constraints--is intimately linked with the ambiguities arising in the quantum theory. Among these ambiguities is the one associated to the SU(2) unitary representation used in the diffeomorphism covariant 'point-splitting' regularization of the nonlinear functionals of the connection. This ambiguity is labeled by a half-integer m and, here, it is referred to as the m ambiguity. The aim of this paper is to investigate the important implications of this ambiguity. We first study 2+1 gravity (and more generally BF theory) quantized in the canonical formulation of loop quantum gravity. Only when the regularization of the quantum constraints is performed in terms of the fundamental representation of the gauge group does one obtain the usual topological quantum field theory as a result. In all other cases unphysical local degrees of freedom arise at the level of the regulated theory that conspire against the existence of the continuum limit. This shows that there is a clear-cut choice in the quantization of the constraints in 2+1 loop quantum gravity. We then analyze the effects of the ambiguity in 3+1 gravity exhibiting the existence of spurious solutions for higher representation quantizations of the Hamiltonian constraint. Although the analysis is not complete in 3+1 dimensions - due to the difficulties associated to the definition of the physical inner product - it provides evidence supporting the definitions quantum dynamics of loop quantum gravity in terms of the fundamental representation of the gauge group as the only consistent possibilities. If the gauge group is SO(3) we find
Effort variation regularization in sound field reproduction
DEFF Research Database (Denmark)
Stefanakis, Nick; Jacobsen, Finn; Sarris, Ioannis
2010-01-01
In this paper, active control is used in order to reproduce a given sound field in an extended spatial region. A method is proposed which minimizes the reproduction error at a number of control positions with the reproduction sources holding a certain relation within their complex strengths......), and adaptive wave field synthesis (AWFS), both under free-field conditions and in reverberant rooms. It is shown that effort variation regularization overcomes the problems associated with small spaces and with a low ratio of direct to reverberant energy, improving thus the reproduction accuracy...
New regularities in mass spectra of hadrons
International Nuclear Information System (INIS)
Kajdalov, A.B.
1989-01-01
The properties of bosonic and baryonic Regge trajectories for hadrons composed of light quarks are considered. Experimental data agree with an existence of daughter trajectories consistent with string models. It is pointed out that the parity doubling for baryonic trajectories, observed experimentally, is not understood in the existing quark models. Mass spectrum of bosons and baryons indicates to an approximate supersymmetry in the mass region M>1 GeV. These regularities indicates to a high degree of symmetry for the dynamics in the confinement region. 8 refs.; 5 figs
Total-variation regularization with bound constraints
International Nuclear Information System (INIS)
Chartrand, Rick; Wohlberg, Brendt
2009-01-01
We present a new algorithm for bound-constrained total-variation (TV) regularization that in comparison with its predecessors is simple, fast, and flexible. We use a splitting approach to decouple TV minimization from enforcing the constraints. Consequently, existing TV solvers can be employed with minimal alteration. This also makes the approach straightforward to generalize to any situation where TV can be applied. We consider deblurring of images with Gaussian or salt-and-pepper noise, as well as Abel inversion of radiographs with Poisson noise. We incorporate previous iterative reweighting algorithms to solve the TV portion.
Bayesian regularization of diffusion tensor images
DEFF Research Database (Denmark)
Frandsen, Jesper; Hobolth, Asger; Østergaard, Leif
2007-01-01
Diffusion tensor imaging (DTI) is a powerful tool in the study of the course of nerve fibre bundles in the human brain. Using DTI, the local fibre orientation in each image voxel can be described by a diffusion tensor which is constructed from local measurements of diffusion coefficients along...... several directions. The measured diffusion coefficients and thereby the diffusion tensors are subject to noise, leading to possibly flawed representations of the three dimensional fibre bundles. In this paper we develop a Bayesian procedure for regularizing the diffusion tensor field, fully utilizing...
Indefinite metric and regularization of electrodynamics
International Nuclear Information System (INIS)
Gaudin, M.
1984-06-01
The invariant regularization of Pauli and Villars in quantum electrodynamics can be considered as deriving from a local and causal lagrangian theory for spin 1/2 bosons, by introducing an indefinite metric and a condition on the allowed states similar to the Lorentz condition. The consequences are the asymptotic freedom of the photon's propagator. We present a calcultion of the effective charge to the fourth order in the coupling as a function of the auxiliary masses, the theory avoiding all mass divergencies to this order [fr
Strategies for regular segmented reductions on GPU
DEFF Research Database (Denmark)
Larsen, Rasmus Wriedt; Henriksen, Troels
2017-01-01
We present and evaluate an implementation technique for regular segmented reductions on GPUs. Existing techniques tend to be either consistent in performance but relatively inefficient in absolute terms, or optimised for specific workloads and thereby exhibiting bad performance for certain input...... is in the context of the Futhark compiler, the implementation technique is applicable to any library or language that has a need for segmented reductions. We evaluate the technique on four microbenchmarks, two of which we also compare to implementations in the CUB library for GPU programming, as well as on two...
Emotion regulation deficits in regular marijuana users.
Zimmermann, Kaeli; Walz, Christina; Derckx, Raissa T; Kendrick, Keith M; Weber, Bernd; Dore, Bruce; Ochsner, Kevin N; Hurlemann, René; Becker, Benjamin
2017-08-01
Effective regulation of negative affective states has been associated with mental health. Impaired regulation of negative affect represents a risk factor for dysfunctional coping mechanisms such as drug use and thus could contribute to the initiation and development of problematic substance use. This study investigated behavioral and neural indices of emotion regulation in regular marijuana users (n = 23) and demographically matched nonusing controls (n = 20) by means of an fMRI cognitive emotion regulation (reappraisal) paradigm. Relative to nonusing controls, marijuana users demonstrated increased neural activity in a bilateral frontal network comprising precentral, middle cingulate, and supplementary motor regions during reappraisal of negative affect (P marijuana users relative to controls. Together, the present findings could reflect an unsuccessful attempt of compensatory recruitment of additional neural resources in the context of disrupted amygdala-prefrontal interaction during volitional emotion regulation in marijuana users. As such, impaired volitional regulation of negative affect might represent a consequence of, or risk factor for, regular marijuana use. Hum Brain Mapp 38:4270-4279, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Efficient multidimensional regularization for Volterra series estimation
Birpoutsoukis, Georgios; Csurcsia, Péter Zoltán; Schoukens, Johan
2018-05-01
This paper presents an efficient nonparametric time domain nonlinear system identification method. It is shown how truncated Volterra series models can be efficiently estimated without the need of long, transient-free measurements. The method is a novel extension of the regularization methods that have been developed for impulse response estimates of linear time invariant systems. To avoid the excessive memory needs in case of long measurements or large number of estimated parameters, a practical gradient-based estimation method is also provided, leading to the same numerical results as the proposed Volterra estimation method. Moreover, the transient effects in the simulated output are removed by a special regularization method based on the novel ideas of transient removal for Linear Time-Varying (LTV) systems. Combining the proposed methodologies, the nonparametric Volterra models of the cascaded water tanks benchmark are presented in this paper. The results for different scenarios varying from a simple Finite Impulse Response (FIR) model to a 3rd degree Volterra series with and without transient removal are compared and studied. It is clear that the obtained models capture the system dynamics when tested on a validation dataset, and their performance is comparable with the white-box (physical) models.
Supporting Regularized Logistic Regression Privately and Efficiently
Li, Wenfa; Liu, Hongzhe; Yang, Peng; Xie, Wei
2016-01-01
As one of the most popular statistical and machine learning models, logistic regression with regularization has found wide adoption in biomedicine, social sciences, information technology, and so on. These domains often involve data of human subjects that are contingent upon strict privacy regulations. Concerns over data privacy make it increasingly difficult to coordinate and conduct large-scale collaborative studies, which typically rely on cross-institution data sharing and joint analysis. Our work here focuses on safeguarding regularized logistic regression, a widely-used statistical model while at the same time has not been investigated from a data security and privacy perspective. We consider a common use scenario of multi-institution collaborative studies, such as in the form of research consortia or networks as widely seen in genetics, epidemiology, social sciences, etc. To make our privacy-enhancing solution practical, we demonstrate a non-conventional and computationally efficient method leveraging distributing computing and strong cryptography to provide comprehensive protection over individual-level and summary data. Extensive empirical evaluations on several studies validate the privacy guarantee, efficiency and scalability of our proposal. We also discuss the practical implications of our solution for large-scale studies and applications from various disciplines, including genetic and biomedical studies, smart grid, network analysis, etc. PMID:27271738
Supporting Regularized Logistic Regression Privately and Efficiently.
Li, Wenfa; Liu, Hongzhe; Yang, Peng; Xie, Wei
2016-01-01
As one of the most popular statistical and machine learning models, logistic regression with regularization has found wide adoption in biomedicine, social sciences, information technology, and so on. These domains often involve data of human subjects that are contingent upon strict privacy regulations. Concerns over data privacy make it increasingly difficult to coordinate and conduct large-scale collaborative studies, which typically rely on cross-institution data sharing and joint analysis. Our work here focuses on safeguarding regularized logistic regression, a widely-used statistical model while at the same time has not been investigated from a data security and privacy perspective. We consider a common use scenario of multi-institution collaborative studies, such as in the form of research consortia or networks as widely seen in genetics, epidemiology, social sciences, etc. To make our privacy-enhancing solution practical, we demonstrate a non-conventional and computationally efficient method leveraging distributing computing and strong cryptography to provide comprehensive protection over individual-level and summary data. Extensive empirical evaluations on several studies validate the privacy guarantee, efficiency and scalability of our proposal. We also discuss the practical implications of our solution for large-scale studies and applications from various disciplines, including genetic and biomedical studies, smart grid, network analysis, etc.
Multiple graph regularized nonnegative matrix factorization
Wang, Jim Jing-Yan
2013-10-01
Non-negative matrix factorization (NMF) has been widely used as a data representation method based on components. To overcome the disadvantage of NMF in failing to consider the manifold structure of a data set, graph regularized NMF (GrNMF) has been proposed by Cai et al. by constructing an affinity graph and searching for a matrix factorization that respects graph structure. Selecting a graph model and its corresponding parameters is critical for this strategy. This process is usually carried out by cross-validation or discrete grid search, which are time consuming and prone to overfitting. In this paper, we propose a GrNMF, called MultiGrNMF, in which the intrinsic manifold is approximated by a linear combination of several graphs with different models and parameters inspired by ensemble manifold regularization. Factorization metrics and linear combination coefficients of graphs are determined simultaneously within a unified object function. They are alternately optimized in an iterative algorithm, thus resulting in a novel data representation algorithm. Extensive experiments on a protein subcellular localization task and an Alzheimer\\'s disease diagnosis task demonstrate the effectiveness of the proposed algorithm. © 2013 Elsevier Ltd. All rights reserved.
Accelerating Large Data Analysis By Exploiting Regularities
Moran, Patrick J.; Ellsworth, David
2003-01-01
We present techniques for discovering and exploiting regularity in large curvilinear data sets. The data can be based on a single mesh or a mesh composed of multiple submeshes (also known as zones). Multi-zone data are typical to Computational Fluid Dynamics (CFD) simulations. Regularities include axis-aligned rectilinear and cylindrical meshes as well as cases where one zone is equivalent to a rigid-body transformation of another. Our algorithms can also discover rigid-body motion of meshes in time-series data. Next, we describe a data model where we can utilize the results from the discovery process in order to accelerate large data visualizations. Where possible, we replace general curvilinear zones with rectilinear or cylindrical zones. In rigid-body motion cases we replace a time-series of meshes with a transformed mesh object where a reference mesh is dynamically transformed based on a given time value in order to satisfy geometry requests, on demand. The data model enables us to make these substitutions and dynamic transformations transparently with respect to the visualization algorithms. We present results with large data sets where we combine our mesh replacement and transformation techniques with out-of-core paging in order to achieve significant speed-ups in analysis.
Supporting Regularized Logistic Regression Privately and Efficiently.
Directory of Open Access Journals (Sweden)
Wenfa Li
Full Text Available As one of the most popular statistical and machine learning models, logistic regression with regularization has found wide adoption in biomedicine, social sciences, information technology, and so on. These domains often involve data of human subjects that are contingent upon strict privacy regulations. Concerns over data privacy make it increasingly difficult to coordinate and conduct large-scale collaborative studies, which typically rely on cross-institution data sharing and joint analysis. Our work here focuses on safeguarding regularized logistic regression, a widely-used statistical model while at the same time has not been investigated from a data security and privacy perspective. We consider a common use scenario of multi-institution collaborative studies, such as in the form of research consortia or networks as widely seen in genetics, epidemiology, social sciences, etc. To make our privacy-enhancing solution practical, we demonstrate a non-conventional and computationally efficient method leveraging distributing computing and strong cryptography to provide comprehensive protection over individual-level and summary data. Extensive empirical evaluations on several studies validate the privacy guarantee, efficiency and scalability of our proposal. We also discuss the practical implications of our solution for large-scale studies and applications from various disciplines, including genetic and biomedical studies, smart grid, network analysis, etc.
Multiview Hessian regularization for image annotation.
Liu, Weifeng; Tao, Dacheng
2013-07-01
The rapid development of computer hardware and Internet technology makes large scale data dependent models computationally tractable, and opens a bright avenue for annotating images through innovative machine learning algorithms. Semisupervised learning (SSL) therefore received intensive attention in recent years and was successfully deployed in image annotation. One representative work in SSL is Laplacian regularization (LR), which smoothes the conditional distribution for classification along the manifold encoded in the graph Laplacian, however, it is observed that LR biases the classification function toward a constant function that possibly results in poor generalization. In addition, LR is developed to handle uniformly distributed data (or single-view data), although instances or objects, such as images and videos, are usually represented by multiview features, such as color, shape, and texture. In this paper, we present multiview Hessian regularization (mHR) to address the above two problems in LR-based image annotation. In particular, mHR optimally combines multiple HR, each of which is obtained from a particular view of instances, and steers the classification function that varies linearly along the data manifold. We apply mHR to kernel least squares and support vector machines as two examples for image annotation. Extensive experiments on the PASCAL VOC'07 dataset validate the effectiveness of mHR by comparing it with baseline algorithms, including LR and HR.
EIT image reconstruction with four dimensional regularization.
Dai, Tao; Soleimani, Manuchehr; Adler, Andy
2008-09-01
Electrical impedance tomography (EIT) reconstructs internal impedance images of the body from electrical measurements on body surface. The temporal resolution of EIT data can be very high, although the spatial resolution of the images is relatively low. Most EIT reconstruction algorithms calculate images from data frames independently, although data are actually highly correlated especially in high speed EIT systems. This paper proposes a 4-D EIT image reconstruction for functional EIT. The new approach is developed to directly use prior models of the temporal correlations among images and 3-D spatial correlations among image elements. A fast algorithm is also developed to reconstruct the regularized images. Image reconstruction is posed in terms of an augmented image and measurement vector which are concatenated from a specific number of previous and future frames. The reconstruction is then based on an augmented regularization matrix which reflects the a priori constraints on temporal and 3-D spatial correlations of image elements. A temporal factor reflecting the relative strength of the image correlation is objectively calculated from measurement data. Results show that image reconstruction models which account for inter-element correlations, in both space and time, show improved resolution and noise performance, in comparison to simpler image models.
Accretion onto some well-known regular black holes
International Nuclear Information System (INIS)
Jawad, Abdul; Shahzad, M.U.
2016-01-01
In this work, we discuss the accretion onto static spherically symmetric regular black holes for specific choices of the equation of state parameter. The underlying regular black holes are charged regular black holes using the Fermi-Dirac distribution, logistic distribution, nonlinear electrodynamics, respectively, and Kehagias-Sftesos asymptotically flat regular black holes. We obtain the critical radius, critical speed, and squared sound speed during the accretion process near the regular black holes. We also study the behavior of radial velocity, energy density, and the rate of change of the mass for each of the regular black holes. (orig.)
Accretion onto some well-known regular black holes
Energy Technology Data Exchange (ETDEWEB)
Jawad, Abdul; Shahzad, M.U. [COMSATS Institute of Information Technology, Department of Mathematics, Lahore (Pakistan)
2016-03-15
In this work, we discuss the accretion onto static spherically symmetric regular black holes for specific choices of the equation of state parameter. The underlying regular black holes are charged regular black holes using the Fermi-Dirac distribution, logistic distribution, nonlinear electrodynamics, respectively, and Kehagias-Sftesos asymptotically flat regular black holes. We obtain the critical radius, critical speed, and squared sound speed during the accretion process near the regular black holes. We also study the behavior of radial velocity, energy density, and the rate of change of the mass for each of the regular black holes. (orig.)
Accretion onto some well-known regular black holes
Jawad, Abdul; Shahzad, M. Umair
2016-03-01
In this work, we discuss the accretion onto static spherically symmetric regular black holes for specific choices of the equation of state parameter. The underlying regular black holes are charged regular black holes using the Fermi-Dirac distribution, logistic distribution, nonlinear electrodynamics, respectively, and Kehagias-Sftesos asymptotically flat regular black holes. We obtain the critical radius, critical speed, and squared sound speed during the accretion process near the regular black holes. We also study the behavior of radial velocity, energy density, and the rate of change of the mass for each of the regular black holes.
CRISPR/Cas9: at the cutting edge of hepatology
Pankowicz, Francis P; Jarrett, Kelsey E; Lagor, William R; Bissig, Karl-Dimiter
2018-01-01
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 genome engineering has revolutionised biomedical science and we are standing on the cusp of medical transformation. The therapeutic potential of this technology is tremendous, however, its translation to the clinic will be challenging. In this article, we review recent progress using this genome editing technology and explore its potential uses in studying and treating diseases of the liver. We discuss the development of new research tools and animal models as well as potential clinical applications, strategies and challenges. PMID:28487442
Hough, Soren H; Ajetunmobi, Ayokunmi; Brody, Leigh; Humphryes-Kirilov, Neil; Perello, Edward
2016-11-01
Desktop Genetics is a bioinformatics company building a gene-editing platform for personalized medicine. The company works with scientists around the world to design and execute state-of-the-art clustered regularly interspaced short palindromic repeats (CRISPR) experiments. Desktop Genetics feeds the lessons learned about experimental intent, single-guide RNA design and data from international genomics projects into a novel CRISPR artificial intelligence system. We believe that machine learning techniques can transform this information into a cognitive therapeutic development tool that will revolutionize medicine.
Use of CRISPR/Cas Genome Editing Technology for Targeted Mutagenesis in Rice.
Xu, Rongfang; Wei, Pengcheng; Yang, Jianbo
2017-01-01
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) system is a newly emerging mutagenesis (gene-editing) tool in genetic engineering. Among the agriculturally important crops, several genes have been successfully mutated by the system, and some agronomic important traits have been rapidly generated, which indicates the potential applications in both scientific research and plant breeding. In this chapter, we describe a standard gene-editing procedure to effectively target rice genes and to make specific rice mutants using the CRISPR/Cas9 system mediated by Agrobacterium transformation.
Cas4 Facilitates PAM-Compatible Spacer Selection during CRISPR Adaptation
Sebastian N. Kieper; Cristóbal Almendros; Juliane Behler; Rebecca E. McKenzie; Franklin L. Nobrega; Anna C. Haagsma; Jochem N.A. Vink; Wolfgang R. Hess; Stan J.J. Brouns
2018-01-01
Summary: CRISPR-Cas systems adapt their immunological memory against their invaders by integrating short DNA fragments into clustered regularly interspaced short palindromic repeat (CRISPR) loci. While Cas1 and Cas2 make up the core machinery of the CRISPR integration process, various class I and II CRISPR-Cas systems encode Cas4 proteins for which the role is unknown. Here, we introduced the CRISPR adaptation genes cas1, cas2, and cas4 from the type I-D CRISPR-Cas system of Synechocystis sp....
Production of genome-edited pluripotent stem cells and mice by CRISPR/Cas.
Horii, Takuro; Hatada, Izuho
2016-01-01
Clustered regularly at interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) nucleases, so-called CRISPR/Cas, was recently developed as an epoch-making genome engineering technology. This system only requires Cas9 nuclease and single-guide RNA complementary to a target locus. CRISPR/Cas enables the generation of knockout cells and animals in a single step. This system can also be used to generate multiple mutations and knockin in a single step, which is not possible using other methods. In this review, we provide an overview of genome editing by CRISPR/Cas in pluripotent stem cells and mice.
CRISPR-Cas9: a promising tool for gene editing on induced pluripotent stem cells.
Kim, Eun Ji; Kang, Ki Ho; Ju, Ji Hyeon
2017-01-01
Recent advances in genome editing with programmable nucleases have opened up new avenues for multiple applications, from basic research to clinical therapy. The ease of use of the technology-and particularly clustered regularly interspaced short palindromic repeats (CRISPR)-will allow us to improve our understanding of genomic variation in disease processes via cellular and animal models. Here, we highlight the progress made in correcting gene mutations in monogenic hereditary disorders and discuss various CRISPR-associated applications, such as cancer research, synthetic biology, and gene therapy using induced pluripotent stem cells. The challenges, ethical issues, and future prospects of CRISPR-based systems for human research are also discussed.
CRISPR/Cas9 for Human Genome Engineering and Disease Research.
Xiong, Xin; Chen, Meng; Lim, Wendell A; Zhao, Dehua; Qi, Lei S
2016-08-31
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system, a versatile RNA-guided DNA targeting platform, has been revolutionizing our ability to modify, manipulate, and visualize the human genome, which greatly advances both biological research and therapeutics development. Here, we review the current development of CRISPR/Cas9 technologies for gene editing, transcription regulation, genome imaging, and epigenetic modification. We discuss the broad application of this system to the study of functional genomics, especially genome-wide genetic screening, and to therapeutics development, including establishing disease models, correcting defective genetic mutations, and treating diseases.
Pliatsika, Venetia; Rigoutsos, Isidore
2015-01-01
Background CRISPR/Cas (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated nucleases) is a powerful component of the prokaryotic immune system that has been adapted for targeted genetic engineering in higher organisms. A key element of CRISPR/Cas is the ?guide? RNA (gRNA) that is ~20 nucleotides (nts) in length and designed to be complementary to the intended target site. An integral requirement of the CRISPR/Cas system is that the target site be followed by a protospa...
Archaeal CRISPR-based immune systems
DEFF Research Database (Denmark)
Garrett, Roger A; Vestergaard, Gisle Alberg; Shah, Shiraz Ali
2011-01-01
CRISPR (clustered regularly interspaced short palindromic repeats)-based immune systems are essentially modular with three primary functions: the excision and integration of new spacers, the processing of CRISPR transcripts to yield mature CRISPR RNAs (crRNAs), and the targeting and cleavage...... of foreign nucleic acid. The primary target appears to be the DNA of foreign genetic elements, but the CRISPR/Cmr system that is widespread amongst archaea also specifically targets and cleaves RNA in vitro. The archaeal CRISPR systems tend to be both diverse and complex. Here we examine evidence...... of CRISPR loci and the evidence for intergenomic exchange of CRISPR systems....
System-level perturbations of cell metabolism using CRISPR/Cas9
Energy Technology Data Exchange (ETDEWEB)
Jakočiūnas, Tadas [Technical Univ. of Denmark, Lyngby (Denmark); Jensen, Michael K. [Technical Univ. of Denmark, Lyngby (Denmark); Keasling, Jay D. [Technical Univ. of Denmark, Lyngby (Denmark); Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States)
2017-03-30
CRISPR/Cas9 (clustered regularly interspaced palindromic repeats and the associated protein Cas9) techniques have made genome engineering and transcriptional reprogramming studies much more advanced and cost-effective. For metabolic engineering purposes, the CRISPR-based tools have been applied to single and multiplex pathway modifications and transcriptional regulations. The effectiveness of these tools allows researchers to implement genome-wide perturbations, test model-guided genome editing strategies, and perform transcriptional reprogramming perturbations in a more advanced manner than previously possible. In this mini-review we highlight recent studies adopting CRISPR/Cas9 for systems-level perturbations and model-guided metabolic engineering.
Control of gene expression by CRISPR-Cas systems
2013-01-01
Clustered regularly interspaced short palindromic repeats (CRISPR) loci and their associated cas (CRISPR-associated) genes provide adaptive immunity against viruses (phages) and other mobile genetic elements in bacteria and archaea. While most of the early work has largely been dominated by examples of CRISPR-Cas systems directing the cleavage of phage or plasmid DNA, recent studies have revealed a more complex landscape where CRISPR-Cas loci might be involved in gene regulation. In this review, we summarize the role of these loci in the regulation of gene expression as well as the recent development of synthetic gene regulation using engineered CRISPR-Cas systems. PMID:24273648
Fan, Xiang-yu; Lin, Yan-ping; Liao, Guo-jian; Xie, Jian-ping
2015-12-01
Zinc finger nuclease, transcription activator-like effector nuclease, and clustered regularly interspaced short palindromic repeats/Cas9 nuclease are important targeted genome editing technologies. They have great significance in scientific research and applications on aspects of functional genomics research, species improvement, disease prevention and gene therapy. There are past or ongoing disputes over ownership of the intellectual property behind every technology. In this review, we summarize the patents on these three targeted genome editing technologies in order to provide some reference for developing genome editing technologies with self-owned intellectual property rights and some implications for current innovation and entrepreneurship education in universities.
Laplacian embedded regression for scalable manifold regularization.
Chen, Lin; Tsang, Ivor W; Xu, Dong
2012-06-01
Semi-supervised learning (SSL), as a powerful tool to learn from a limited number of labeled data and a large number of unlabeled data, has been attracting increasing attention in the machine learning community. In particular, the manifold regularization framework has laid solid theoretical foundations for a large family of SSL algorithms, such as Laplacian support vector machine (LapSVM) and Laplacian regularized least squares (LapRLS). However, most of these algorithms are limited to small scale problems due to the high computational cost of the matrix inversion operation involved in the optimization problem. In this paper, we propose a novel framework called Laplacian embedded regression by introducing an intermediate decision variable into the manifold regularization framework. By using ∈-insensitive loss, we obtain the Laplacian embedded support vector regression (LapESVR) algorithm, which inherits the sparse solution from SVR. Also, we derive Laplacian embedded RLS (LapERLS) corresponding to RLS under the proposed framework. Both LapESVR and LapERLS possess a simpler form of a transformed kernel, which is the summation of the original kernel and a graph kernel that captures the manifold structure. The benefits of the transformed kernel are two-fold: (1) we can deal with the original kernel matrix and the graph Laplacian matrix in the graph kernel separately and (2) if the graph Laplacian matrix is sparse, we only need to perform the inverse operation for a sparse matrix, which is much more efficient when compared with that for a dense one. Inspired by kernel principal component analysis, we further propose to project the introduced decision variable into a subspace spanned by a few eigenvectors of the graph Laplacian matrix in order to better reflect the data manifold, as well as accelerate the calculation of the graph kernel, allowing our methods to efficiently and effectively cope with large scale SSL problems. Extensive experiments on both toy and real
Constrained least squares regularization in PET
International Nuclear Information System (INIS)
Choudhury, K.R.; O'Sullivan, F.O.
1996-01-01
Standard reconstruction methods used in tomography produce images with undesirable negative artifacts in background and in areas of high local contrast. While sophisticated statistical reconstruction methods can be devised to correct for these artifacts, their computational implementation is excessive for routine operational use. This work describes a technique for rapid computation of approximate constrained least squares regularization estimates. The unique feature of the approach is that it involves no iterative projection or backprojection steps. This contrasts with the familiar computationally intensive algorithms based on algebraic reconstruction (ART) or expectation-maximization (EM) methods. Experimentation with the new approach for deconvolution and mixture analysis shows that the root mean square error quality of estimators based on the proposed algorithm matches and usually dominates that of more elaborate maximum likelihood, at a fraction of the computational effort
Regularities of radiorace formation in yeasts
International Nuclear Information System (INIS)
Korogodin, V.I.; Bliznik, K.M.; Kapul'tsevich, Yu.G.; Petin, V.G.; Akademiya Meditsinskikh Nauk SSSR, Obninsk. Nauchno-Issledovatel'skij Inst. Meditsinskoj Radiologii)
1977-01-01
Two strains of diploid yeast, namely, Saccharomyces ellipsoides, Megri 139-B, isolated under natural conditions, and Saccharomyces cerevisiae 5a x 3Bα, heterozygous by genes ade 1 and ade 2, were exposed to γ-quanta of Co 60 . The content of cells-saltants forming colonies with changed morphology, that of the nonviable cells, cells that are respiration mutants, and cells-recombinants by gene ade 1 and ade 2, has been determined. A certain regularity has been revealed in the distribution among the colonies of cells of the four types mentioned above: the higher the content of cells of some one of the types, the higher that of the cells having other hereditary changes
Regularization destriping of remote sensing imagery
Basnayake, Ranil; Bollt, Erik; Tufillaro, Nicholas; Sun, Jie; Gierach, Michelle
2017-07-01
We illustrate the utility of variational destriping for ocean color images from both multispectral and hyperspectral sensors. In particular, we examine data from a filter spectrometer, the Visible Infrared Imaging Radiometer Suite (VIIRS) on the Suomi National Polar Partnership (NPP) orbiter, and an airborne grating spectrometer, the Jet Population Laboratory's (JPL) hyperspectral Portable Remote Imaging Spectrometer (PRISM) sensor. We solve the destriping problem using a variational regularization method by giving weights spatially to preserve the other features of the image during the destriping process. The target functional penalizes the neighborhood of stripes (strictly, directionally uniform features) while promoting data fidelity, and the functional is minimized by solving the Euler-Lagrange equations with an explicit finite-difference scheme. We show the accuracy of our method from a benchmark data set which represents the sea surface temperature off the coast of Oregon, USA. Technical details, such as how to impose continuity across data gaps using inpainting, are also described.
The Regularity of Optimal Irrigation Patterns
Morel, Jean-Michel; Santambrogio, Filippo
2010-02-01
A branched structure is observable in draining and irrigation systems, in electric power supply systems, and in natural objects like blood vessels, the river basins or the trees. Recent approaches of these networks derive their branched structure from an energy functional whose essential feature is to favor wide routes. Given a flow s in a river, a road, a tube or a wire, the transportation cost per unit length is supposed in these models to be proportional to s α with 0 measure is the Lebesgue density on a smooth open set and the irrigating measure is a single source. In that case we prove that all branches of optimal irrigation trees satisfy an elliptic equation and that their curvature is a bounded measure. In consequence all branching points in the network have a tangent cone made of a finite number of segments, and all other points have a tangent. An explicit counterexample disproves these regularity properties for non-Lebesgue irrigated measures.
Singular tachyon kinks from regular profiles
International Nuclear Information System (INIS)
Copeland, E.J.; Saffin, P.M.; Steer, D.A.
2003-01-01
We demonstrate how Sen's singular kink solution of the Born-Infeld tachyon action can be constructed by taking the appropriate limit of initially regular profiles. It is shown that the order in which different limits are taken plays an important role in determining whether or not such a solution is obtained for a wide class of potentials. Indeed, by introducing a small parameter into the action, we are able circumvent the results of a recent paper which derived two conditions on the asymptotic tachyon potential such that the singular kink could be recovered in the large amplitude limit of periodic solutions. We show that this is explained by the non-commuting nature of two limits, and that Sen's solution is recovered if the order of the limits is chosen appropriately
Two-pass greedy regular expression parsing
DEFF Research Database (Denmark)
Grathwohl, Niels Bjørn Bugge; Henglein, Fritz; Nielsen, Lasse
2013-01-01
We present new algorithms for producing greedy parses for regular expressions (REs) in a semi-streaming fashion. Our lean-log algorithm executes in time O(mn) for REs of size m and input strings of size n and outputs a compact bit-coded parse tree representation. It improves on previous algorithms...... by: operating in only 2 passes; using only O(m) words of random-access memory (independent of n); requiring only kn bits of sequentially written and read log storage, where k ... and not requiring it to be stored at all. Previous RE parsing algorithms do not scale linearly with input size, or require substantially more log storage and employ 3 passes where the first consists of reversing the input, or do not or are not known to produce a greedy parse. The performance of our unoptimized C...
Discriminative Elastic-Net Regularized Linear Regression.
Zhang, Zheng; Lai, Zhihui; Xu, Yong; Shao, Ling; Wu, Jian; Xie, Guo-Sen
2017-03-01
In this paper, we aim at learning compact and discriminative linear regression models. Linear regression has been widely used in different problems. However, most of the existing linear regression methods exploit the conventional zero-one matrix as the regression targets, which greatly narrows the flexibility of the regression model. Another major limitation of these methods is that the learned projection matrix fails to precisely project the image features to the target space due to their weak discriminative capability. To this end, we present an elastic-net regularized linear regression (ENLR) framework, and develop two robust linear regression models which possess the following special characteristics. First, our methods exploit two particular strategies to enlarge the margins of different classes by relaxing the strict binary targets into a more feasible variable matrix. Second, a robust elastic-net regularization of singular values is introduced to enhance the compactness and effectiveness of the learned projection matrix. Third, the resulting optimization problem of ENLR has a closed-form solution in each iteration, which can be solved efficiently. Finally, rather than directly exploiting the projection matrix for recognition, our methods employ the transformed features as the new discriminate representations to make final image classification. Compared with the traditional linear regression model and some of its variants, our method is much more accurate in image classification. Extensive experiments conducted on publicly available data sets well demonstrate that the proposed framework can outperform the state-of-the-art methods. The MATLAB codes of our methods can be available at http://www.yongxu.org/lunwen.html.
Regularization of Instantaneous Frequency Attribute Computations
Yedlin, M. J.; Margrave, G. F.; Van Vorst, D. G.; Ben Horin, Y.
2014-12-01
We compare two different methods of computation of a temporally local frequency:1) A stabilized instantaneous frequency using the theory of the analytic signal.2) A temporally variant centroid (or dominant) frequency estimated from a time-frequency decomposition.The first method derives from Taner et al (1979) as modified by Fomel (2007) and utilizes the derivative of the instantaneous phase of the analytic signal. The second method computes the power centroid (Cohen, 1995) of the time-frequency spectrum, obtained using either the Gabor or Stockwell Transform. Common to both methods is the necessity of division by a diagonal matrix, which requires appropriate regularization.We modify Fomel's (2007) method by explicitly penalizing the roughness of the estimate. Following Farquharson and Oldenburg (2004), we employ both the L curve and GCV methods to obtain the smoothest model that fits the data in the L2 norm.Using synthetic data, quarry blast, earthquakes and the DPRK tests, our results suggest that the optimal method depends on the data. One of the main applications for this work is the discrimination between blast events and earthquakesFomel, Sergey. " Local seismic attributes." , Geophysics, 72.3 (2007): A29-A33.Cohen, Leon. " Time frequency analysis theory and applications." USA: Prentice Hall, (1995).Farquharson, Colin G., and Douglas W. Oldenburg. "A comparison of automatic techniques for estimating the regularization parameter in non-linear inverse problems." Geophysical Journal International 156.3 (2004): 411-425.Taner, M. Turhan, Fulton Koehler, and R. E. Sheriff. " Complex seismic trace analysis." Geophysics, 44.6 (1979): 1041-1063.
Regularized Regression and Density Estimation based on Optimal Transport
Burger, M.; Franek, M.; Schonlieb, C.-B.
2012-01-01
for estimating densities and for preserving edges in the case of total variation regularization. In order to compute solutions of the variational problems, a regularized optimal transport problem needs to be solved, for which we discuss several formulations
Incremental projection approach of regularization for inverse problems
Energy Technology Data Exchange (ETDEWEB)
Souopgui, Innocent, E-mail: innocent.souopgui@usm.edu [The University of Southern Mississippi, Department of Marine Science (United States); Ngodock, Hans E., E-mail: hans.ngodock@nrlssc.navy.mil [Naval Research Laboratory (United States); Vidard, Arthur, E-mail: arthur.vidard@imag.fr; Le Dimet, François-Xavier, E-mail: ledimet@imag.fr [Laboratoire Jean Kuntzmann (France)
2016-10-15
This paper presents an alternative approach to the regularized least squares solution of ill-posed inverse problems. Instead of solving a minimization problem with an objective function composed of a data term and a regularization term, the regularization information is used to define a projection onto a convex subspace of regularized candidate solutions. The objective function is modified to include the projection of each iterate in the place of the regularization. Numerical experiments based on the problem of motion estimation for geophysical fluid images, show the improvement of the proposed method compared with regularization methods. For the presented test case, the incremental projection method uses 7 times less computation time than the regularization method, to reach the same error target. Moreover, at convergence, the incremental projection is two order of magnitude more accurate than the regularization method.
Dimensional regularization and analytical continuation at finite temperature
International Nuclear Information System (INIS)
Chen Xiangjun; Liu Lianshou
1998-01-01
The relationship between dimensional regularization and analytical continuation of infrared divergent integrals at finite temperature is discussed and a method of regularization of infrared divergent integrals and infrared divergent sums is given
Bounded Perturbation Regularization for Linear Least Squares Estimation
Ballal, Tarig; Suliman, Mohamed Abdalla Elhag; Al-Naffouri, Tareq Y.
2017-01-01
This paper addresses the problem of selecting the regularization parameter for linear least-squares estimation. We propose a new technique called bounded perturbation regularization (BPR). In the proposed BPR method, a perturbation with a bounded
Regular Generalized Star Star closed sets in Bitopological Spaces
K. Kannan; D. Narasimhan; K. Chandrasekhara Rao; R. Ravikumar
2011-01-01
The aim of this paper is to introduce the concepts of τ1τ2-regular generalized star star closed sets , τ1τ2-regular generalized star star open sets and study their basic properties in bitopological spaces.
Exclusion of children with intellectual disabilities from regular ...
African Journals Online (AJOL)
Study investigated why teachers exclude children with intellectual disability from the regular classrooms in Nigeria. Participants were, 169 regular teachers randomly selected from Oyo and Ogun states. Questionnaire was used to collect data result revealed that 57.4% regular teachers could not cope with children with ID ...
39 CFR 6.1 - Regular meetings, annual meeting.
2010-07-01
... 39 Postal Service 1 2010-07-01 2010-07-01 false Regular meetings, annual meeting. 6.1 Section 6.1 Postal Service UNITED STATES POSTAL SERVICE THE BOARD OF GOVERNORS OF THE U.S. POSTAL SERVICE MEETINGS (ARTICLE VI) § 6.1 Regular meetings, annual meeting. The Board shall meet regularly on a schedule...
Recognition Memory for Novel Stimuli: The Structural Regularity Hypothesis
Cleary, Anne M.; Morris, Alison L.; Langley, Moses M.
2007-01-01
Early studies of human memory suggest that adherence to a known structural regularity (e.g., orthographic regularity) benefits memory for an otherwise novel stimulus (e.g., G. A. Miller, 1958). However, a more recent study suggests that structural regularity can lead to an increase in false-positive responses on recognition memory tests (B. W. A.…
5 CFR 551.421 - Regular working hours.
2010-01-01
... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Regular working hours. 551.421 Section... Activities § 551.421 Regular working hours. (a) Under the Act there is no requirement that a Federal employee... distinction based on whether the activity is performed by an employee during regular working hours or outside...
20 CFR 226.35 - Deductions from regular annuity rate.
2010-04-01
... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Deductions from regular annuity rate. 226.35... COMPUTING EMPLOYEE, SPOUSE, AND DIVORCED SPOUSE ANNUITIES Computing a Spouse or Divorced Spouse Annuity § 226.35 Deductions from regular annuity rate. The regular annuity rate of the spouse and divorced...
20 CFR 226.34 - Divorced spouse regular annuity rate.
2010-04-01
... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Divorced spouse regular annuity rate. 226.34... COMPUTING EMPLOYEE, SPOUSE, AND DIVORCED SPOUSE ANNUITIES Computing a Spouse or Divorced Spouse Annuity § 226.34 Divorced spouse regular annuity rate. The regular annuity rate of a divorced spouse is equal to...
20 CFR 226.14 - Employee regular annuity rate.
2010-04-01
... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Employee regular annuity rate. 226.14 Section... COMPUTING EMPLOYEE, SPOUSE, AND DIVORCED SPOUSE ANNUITIES Computing an Employee Annuity § 226.14 Employee regular annuity rate. The regular annuity rate payable to the employee is the total of the employee tier I...
Accreting fluids onto regular black holes via Hamiltonian approach
Energy Technology Data Exchange (ETDEWEB)
Jawad, Abdul [COMSATS Institute of Information Technology, Department of Mathematics, Lahore (Pakistan); Shahzad, M.U. [COMSATS Institute of Information Technology, Department of Mathematics, Lahore (Pakistan); University of Central Punjab, CAMS, UCP Business School, Lahore (Pakistan)
2017-08-15
We investigate the accretion of test fluids onto regular black holes such as Kehagias-Sfetsos black holes and regular black holes with Dagum distribution function. We analyze the accretion process when different test fluids are falling onto these regular black holes. The accreting fluid is being classified through the equation of state according to the features of regular black holes. The behavior of fluid flow and the existence of sonic points is being checked for these regular black holes. It is noted that the three-velocity depends on critical points and the equation of state parameter on phase space. (orig.)
On the regularized fermionic projector of the vacuum
Finster, Felix
2008-03-01
We construct families of fermionic projectors with spherically symmetric regularization, which satisfy the condition of a distributional MP-product. The method is to analyze regularization tails with a power law or logarithmic scaling in composite expressions in the fermionic projector. The resulting regularizations break the Lorentz symmetry and give rise to a multilayer structure of the fermionic projector near the light cone. Furthermore, we construct regularizations which go beyond the distributional MP-product in that they yield additional distributional contributions supported at the origin. The remaining freedom for the regularization parameters and the consequences for the normalization of the fermionic states are discussed.
On the regularized fermionic projector of the vacuum
International Nuclear Information System (INIS)
Finster, Felix
2008-01-01
We construct families of fermionic projectors with spherically symmetric regularization, which satisfy the condition of a distributional MP-product. The method is to analyze regularization tails with a power law or logarithmic scaling in composite expressions in the fermionic projector. The resulting regularizations break the Lorentz symmetry and give rise to a multilayer structure of the fermionic projector near the light cone. Furthermore, we construct regularizations which go beyond the distributional MP-product in that they yield additional distributional contributions supported at the origin. The remaining freedom for the regularization parameters and the consequences for the normalization of the fermionic states are discussed
MRI reconstruction with joint global regularization and transform learning.
Tanc, A Korhan; Eksioglu, Ender M
2016-10-01
Sparsity based regularization has been a popular approach to remedy the measurement scarcity in image reconstruction. Recently, sparsifying transforms learned from image patches have been utilized as an effective regularizer for the Magnetic Resonance Imaging (MRI) reconstruction. Here, we infuse additional global regularization terms to the patch-based transform learning. We develop an algorithm to solve the resulting novel cost function, which includes both patchwise and global regularization terms. Extensive simulation results indicate that the introduced mixed approach has improved MRI reconstruction performance, when compared to the algorithms which use either of the patchwise transform learning or global regularization terms alone. Copyright © 2016 Elsevier Ltd. All rights reserved.
Manifold Regularized Experimental Design for Active Learning.
Zhang, Lining; Shum, Hubert P H; Shao, Ling
2016-12-02
Various machine learning and data mining tasks in classification require abundant data samples to be labeled for training. Conventional active learning methods aim at labeling the most informative samples for alleviating the labor of the user. Many previous studies in active learning select one sample after another in a greedy manner. However, this is not very effective because the classification models has to be retrained for each newly labeled sample. Moreover, many popular active learning approaches utilize the most uncertain samples by leveraging the classification hyperplane of the classifier, which is not appropriate since the classification hyperplane is inaccurate when the training data are small-sized. The problem of insufficient training data in real-world systems limits the potential applications of these approaches. This paper presents a novel method of active learning called manifold regularized experimental design (MRED), which can label multiple informative samples at one time for training. In addition, MRED gives an explicit geometric explanation for the selected samples to be labeled by the user. Different from existing active learning methods, our method avoids the intrinsic problems caused by insufficiently labeled samples in real-world applications. Various experiments on synthetic datasets, the Yale face database and the Corel image database have been carried out to show how MRED outperforms existing methods.
Regularization of the Coulomb scattering problem
International Nuclear Information System (INIS)
Baryshevskii, V.G.; Feranchuk, I.D.; Kats, P.B.
2004-01-01
The exact solution of the Schroedinger equation for the Coulomb potential is used within the scope of both stationary and time-dependent scattering theories in order to find the parameters which determine the regularization of the Rutherford cross section when the scattering angle tends to zero but the distance r from the center remains finite. The angular distribution of the particles scattered in the Coulomb field is studied on rather a large but finite distance r from the center. It is shown that the standard asymptotic representation of the wave functions is inapplicable in the case when small scattering angles are considered. The unitary property of the scattering matrix is analyzed and the 'optical' theorem for this case is discussed. The total and transport cross sections for scattering the particle by the Coulomb center proved to be finite values and are calculated in the analytical form. It is shown that the effects under consideration can be important for the observed characteristics of the transport processes in semiconductors which are determined by the electron and hole scattering by the field of charged impurity centers
Color correction optimization with hue regularization
Zhang, Heng; Liu, Huaping; Quan, Shuxue
2011-01-01
Previous work has suggested that observers are capable of judging the quality of an image without any knowledge of the original scene. When no reference is available, observers can extract the apparent objects in an image and compare them with the typical colors of similar objects recalled from their memories. Some generally agreed upon research results indicate that although perfect colorimetric rendering is not conspicuous and color errors can be well tolerated, the appropriate rendition of certain memory colors such as skin, grass, and sky is an important factor in the overall perceived image quality. These colors are appreciated in a fairly consistent manner and are memorized with slightly different hues and higher color saturation. The aim of color correction for a digital color pipeline is to transform the image data from a device dependent color space to a target color space, usually through a color correction matrix which in its most basic form is optimized through linear regressions between the two sets of data in two color spaces in the sense of minimized Euclidean color error. Unfortunately, this method could result in objectionable distortions if the color error biased certain colors undesirably. In this paper, we propose a color correction optimization method with preferred color reproduction in mind through hue regularization and present some experimental results.
Wave dynamics of regular and chaotic rays
International Nuclear Information System (INIS)
McDonald, S.W.
1983-09-01
In order to investigate general relationships between waves and rays in chaotic systems, I study the eigenfunctions and spectrum of a simple model, the two-dimensional Helmholtz equation in a stadium boundary, for which the rays are ergodic. Statistical measurements are performed so that the apparent randomness of the stadium modes can be quantitatively contrasted with the familiar regularities observed for the modes in a circular boundary (with integrable rays). The local spatial autocorrelation of the eigenfunctions is constructed in order to indirectly test theoretical predictions for the nature of the Wigner distribution corresponding to chaotic waves. A portion of the large-eigenvalue spectrum is computed and reported in an appendix; the probability distribution of successive level spacings is analyzed and compared with theoretical predictions. The two principal conclusions are: 1) waves associated with chaotic rays may exhibit randomly situated localized regions of high intensity; 2) the Wigner function for these waves may depart significantly from being uniformly distributed over the surface of constant frequency in the ray phase space
Regularities and irregularities in order flow data
Theissen, Martin; Krause, Sebastian M.; Guhr, Thomas
2017-11-01
We identify and analyze statistical regularities and irregularities in the recent order flow of different NASDAQ stocks, focusing on the positions where orders are placed in the order book. This includes limit orders being placed outside of the spread, inside the spread and (effective) market orders. Based on the pairwise comparison of the order flow of different stocks, we perform a clustering of stocks into groups with similar behavior. This is useful to assess systemic aspects of stock price dynamics. We find that limit order placement inside the spread is strongly determined by the dynamics of the spread size. Most orders, however, arrive outside of the spread. While for some stocks order placement on or next to the quotes is dominating, deeper price levels are more important for other stocks. As market orders are usually adjusted to the quote volume, the impact of market orders depends on the order book structure, which we find to be quite diverse among the analyzed stocks as a result of the way limit order placement takes place.
Library search with regular reflectance IR spectra
International Nuclear Information System (INIS)
Staat, H.; Korte, E.H.; Lampen, P.
1989-01-01
Characterisation in situ for coatings and other surface layers is generally favourable, but a prerequisite for precious items such as art objects. In infrared spectroscopy only reflection techniques are applicable here. However for attenuated total reflection (ATR) it is difficult to obtain the necessary optical contact of the crystal with the sample, when the latter is not perfectly plane or flexible. The measurement of diffuse reflectance demands a scattering sample and usually the reflectance is very poor. Therefore in most cases one is left with regular reflectance. Such spectra consist of dispersion-like feature instead of bands impeding their interpretation in the way the analyst is used to. Furthermore for computer search in common spectral libraries compiled from transmittance or absorbance spectra a transformation of the reflectance spectra is needed. The correct conversion is based on the Kramers-Kronig transformation. This somewhat time - consuming procedure can be speeded up by using appropriate approximations. A coarser conversion may be obtained from the first derivative of the reflectance spectrum which resembles the second derivative of a transmittance spectrum. The resulting distorted spectra can still be used successfully for the search in peak table libraries. Experiences with both transformations are presented. (author)
Regularities of praseodymium oxide dissolution in acids
International Nuclear Information System (INIS)
Savin, V.D.; Elyutin, A.V.; Mikhajlova, N.P.; Eremenko, Z.V.; Opolchenova, N.L.
1989-01-01
The regularities of Pr 2 O 3 , Pr 2 O 5 and Pr(OH) 3 interaction with inorganic acids are studied. pH of the solution and oxidation-reduction potential registrated at 20±1 deg C are the working parameters of studies. It is found that the amount of all oxides dissolved increase in the series of acids - nitric, hydrochloric and sulfuric, in this case for hydrochloric and sulfuric acid it increases in the series of oxides Pr 2 O 3 , Pr 2 O 5 and Pr(OH) 3 . It is noted that Pr 2 O 5 has a high value of oxidation-reduction potential with a positive sign in the whole disslolving range. A low positive value of a redox potential during dissolving belongs to Pr(OH) 3 and in the case of Pr 2 O 3 dissloving redox potential is negative. The schemes of dissolving processes which do not agree with classical assumptions are presented
Regular expressions compiler and some applications
International Nuclear Information System (INIS)
Saldana A, H.
1978-01-01
We deal with high level programming language of a Regular Expressions Compiler (REC). The first chapter is an introduction in which the history of the REC development and the problems related to its numerous applicatons are described. The syntactic and sematic rules as well as the language features are discussed just after the introduction. Concerning the applicatons as examples, an adaptation is given in order to solve numerical problems and another for the data manipulation. The last chapter is an exposition of ideas and techniques about the compiler construction. Examples of the adaptation to numerical problems show the applications to education, vector analysis, quantum mechanics, physics, mathematics and other sciences. The rudiments of an operating system for a minicomputer are the examples of the adaptation to symbolic data manipulaton. REC is a programming language that could be applied to solve problems in almost any human activity. Handling of computer graphics, control equipment, research on languages, microprocessors and general research are some of the fields in which this programming language can be applied and developed. (author)
Sparsity-regularized HMAX for visual recognition.
Directory of Open Access Journals (Sweden)
Xiaolin Hu
Full Text Available About ten years ago, HMAX was proposed as a simple and biologically feasible model for object recognition, based on how the visual cortex processes information. However, the model does not encompass sparse firing, which is a hallmark of neurons at all stages of the visual pathway. The current paper presents an improved model, called sparse HMAX, which integrates sparse firing. This model is able to learn higher-level features of objects on unlabeled training images. Unlike most other deep learning models that explicitly address global structure of images in every layer, sparse HMAX addresses local to global structure gradually along the hierarchy by applying patch-based learning to the output of the previous layer. As a consequence, the learning method can be standard sparse coding (SSC or independent component analysis (ICA, two techniques deeply rooted in neuroscience. What makes SSC and ICA applicable at higher levels is the introduction of linear higher-order statistical regularities by max pooling. After training, high-level units display sparse, invariant selectivity for particular individuals or for image categories like those observed in human inferior temporal cortex (ITC and medial temporal lobe (MTL. Finally, on an image classification benchmark, sparse HMAX outperforms the original HMAX by a large margin, suggesting its great potential for computer vision.
Quantum implications of a scale invariant regularization
Ghilencea, D. M.
2018-04-01
We study scale invariance at the quantum level in a perturbative approach. For a scale-invariant classical theory, the scalar potential is computed at a three-loop level while keeping manifest this symmetry. Spontaneous scale symmetry breaking is transmitted at a quantum level to the visible sector (of ϕ ) by the associated Goldstone mode (dilaton σ ), which enables a scale-invariant regularization and whose vacuum expectation value ⟨σ ⟩ generates the subtraction scale (μ ). While the hidden (σ ) and visible sector (ϕ ) are classically decoupled in d =4 due to an enhanced Poincaré symmetry, they interact through (a series of) evanescent couplings ∝ɛ , dictated by the scale invariance of the action in d =4 -2 ɛ . At the quantum level, these couplings generate new corrections to the potential, as scale-invariant nonpolynomial effective operators ϕ2 n +4/σ2 n. These are comparable in size to "standard" loop corrections and are important for values of ϕ close to ⟨σ ⟩. For n =1 , 2, the beta functions of their coefficient are computed at three loops. In the IR limit, dilaton fluctuations decouple, the effective operators are suppressed by large ⟨σ ⟩, and the effective potential becomes that of a renormalizable theory with explicit scale symmetry breaking by the DR scheme (of μ =constant).
Regularities development of entrepreneurial structures in regions
Directory of Open Access Journals (Sweden)
Julia Semenovna Pinkovetskaya
2012-12-01
Full Text Available Consider regularities and tendencies for the three types of entrepreneurial structures — small enterprises, medium enterprises and individual entrepreneurs. The aim of the research was to confirm the possibilities of describing indicators of aggregate entrepreneurial structures with the use of normal law distribution functions. Presented proposed by the author the methodological approach and results of construction of the functions of the density distribution for the main indicators for the various objects: the Russian Federation, regions, as well as aggregates ofentrepreneurial structures, specialized in certain forms ofeconomic activity. All the developed functions, as shown by the logical and statistical analysis, are of high quality and well-approximate the original data. In general, the proposed methodological approach is versatile and can be used in further studies of aggregates of entrepreneurial structures. The received results can be applied in solving a wide range of problems justify the need for personnel and financial resources at the federal, regional and municipal levels, as well as the formation of plans and forecasts of development entrepreneurship and improvement of this sector of the economy.
TRANSIENT LUNAR PHENOMENA: REGULARITY AND REALITY
International Nuclear Information System (INIS)
Crotts, Arlin P. S.
2009-01-01
Transient lunar phenomena (TLPs) have been reported for centuries, but their nature is largely unsettled, and even their existence as a coherent phenomenon is controversial. Nonetheless, TLP data show regularities in the observations; a key question is whether this structure is imposed by processes tied to the lunar surface, or by terrestrial atmospheric or human observer effects. I interrogate an extensive catalog of TLPs to gauge how human factors determine the distribution of TLP reports. The sample is grouped according to variables which should produce differing results if determining factors involve humans, and not reflecting phenomena tied to the lunar surface. Features dependent on human factors can then be excluded. Regardless of how the sample is split, the results are similar: ∼50% of reports originate from near Aristarchus, ∼16% from Plato, ∼6% from recent, major impacts (Copernicus, Kepler, Tycho, and Aristarchus), plus several at Grimaldi. Mare Crisium produces a robust signal in some cases (however, Crisium is too large for a 'feature' as defined). TLP count consistency for these features indicates that ∼80% of these may be real. Some commonly reported sites disappear from the robust averages, including Alphonsus, Ross D, and Gassendi. These reports begin almost exclusively after 1955, when TLPs became widely known and many more (and inexperienced) observers searched for TLPs. In a companion paper, we compare the spatial distribution of robust TLP sites to transient outgassing (seen by Apollo and Lunar Prospector instruments). To a high confidence, robust TLP sites and those of lunar outgassing correlate strongly, further arguing for the reality of TLPs.
Elementary Particle Spectroscopy in Regular Solid Rewrite
International Nuclear Information System (INIS)
Trell, Erik
2008-01-01
The Nilpotent Universal Computer Rewrite System (NUCRS) has operationalized the radical ontological dilemma of Nothing at All versus Anything at All down to the ground recursive syntax and principal mathematical realisation of this categorical dichotomy as such and so governing all its sui generis modalities, leading to fulfilment of their individual terms and compass when the respective choice sequence operations are brought to closure. Focussing on the general grammar, NUCRS by pure logic and its algebraic notations hence bootstraps Quantum Mechanics, aware that it ''is the likely keystone of a fundamental computational foundation'' also for e.g. physics, molecular biology and neuroscience. The present work deals with classical geometry where morphology is the modality, and ventures that the ancient regular solids are its specific rewrite system, in effect extensively anticipating the detailed elementary particle spectroscopy, and further on to essential structures at large both over the inorganic and organic realms. The geodetic antipode to Nothing is extension, with natural eigenvector the endless straight line which when deployed according to the NUCRS as well as Plotelemeian topographic prescriptions forms a real three-dimensional eigenspace with cubical eigenelements where observed quark-skewed quantum-chromodynamical particle events self-generate as an Aristotelean phase transition between the straight and round extremes of absolute endlessness under the symmetry- and gauge-preserving, canonical coset decomposition SO(3)xO(5) of Lie algebra SU(3). The cubical eigen-space and eigen-elements are the parental state and frame, and the other solids are a range of transition matrix elements and portions adapting to the spherical root vector symmetries and so reproducibly reproducing the elementary particle spectroscopy, including a modular, truncated octahedron nano-composition of the Electron which piecemeal enter into molecular structures or compressed to each
Regularization of plurisubharmonic functions with a net of good points
Li, Long
2017-01-01
The purpose of this article is to present a new regularization technique of quasi-plurisubharmoinc functions on a compact Kaehler manifold. The idea is to regularize the function on local coordinate balls first, and then glue each piece together. Therefore, all the higher order terms in the complex Hessian of this regularization vanish at the center of each coordinate ball, and all the centers build a delta-net of the manifold eventually.
International Nuclear Information System (INIS)
Keller, Kai Johannes
2010-04-01
The present work contains a consistent formulation of the methods of dimensional regularization (DimReg) and minimal subtraction (MS) in Minkowski position space. The methods are implemented into the framework of perturbative Algebraic Quantum Field Theory (pAQFT). The developed methods are used to solve the Epstein-Glaser recursion for the construction of time-ordered products in all orders of causal perturbation theory. A solution is given in terms of a forest formula in the sense of Zimmermann. A relation to the alternative approach to renormalization theory using Hopf algebras is established. (orig.)
Energy Technology Data Exchange (ETDEWEB)
Keller, Kai Johannes
2010-04-15
The present work contains a consistent formulation of the methods of dimensional regularization (DimReg) and minimal subtraction (MS) in Minkowski position space. The methods are implemented into the framework of perturbative Algebraic Quantum Field Theory (pAQFT). The developed methods are used to solve the Epstein-Glaser recursion for the construction of time-ordered products in all orders of causal perturbation theory. A solution is given in terms of a forest formula in the sense of Zimmermann. A relation to the alternative approach to renormalization theory using Hopf algebras is established. (orig.)
Higher order total variation regularization for EIT reconstruction.
Gong, Bo; Schullcke, Benjamin; Krueger-Ziolek, Sabine; Zhang, Fan; Mueller-Lisse, Ullrich; Moeller, Knut
2018-01-08
Electrical impedance tomography (EIT) attempts to reveal the conductivity distribution of a domain based on the electrical boundary condition. This is an ill-posed inverse problem; its solution is very unstable. Total variation (TV) regularization is one of the techniques commonly employed to stabilize reconstructions. However, it is well known that TV regularization induces staircase effects, which are not realistic in clinical applications. To reduce such artifacts, modified TV regularization terms considering a higher order differential operator were developed in several previous studies. One of them is called total generalized variation (TGV) regularization. TGV regularization has been successively applied in image processing in a regular grid context. In this study, we adapted TGV regularization to the finite element model (FEM) framework for EIT reconstruction. Reconstructions using simulation and clinical data were performed. First results indicate that, in comparison to TV regularization, TGV regularization promotes more realistic images. Graphical abstract Reconstructed conductivity changes located on selected vertical lines. For each of the reconstructed images as well as the ground truth image, conductivity changes located along the selected left and right vertical lines are plotted. In these plots, the notation GT in the legend stands for ground truth, TV stands for total variation method, and TGV stands for total generalized variation method. Reconstructed conductivity distributions from the GREIT algorithm are also demonstrated.
Regular Breakfast and Blood Lead Levels among Preschool Children
Directory of Open Access Journals (Sweden)
Needleman Herbert
2011-04-01
Full Text Available Abstract Background Previous studies have shown that fasting increases lead absorption in the gastrointestinal tract of adults. Regular meals/snacks are recommended as a nutritional intervention for lead poisoning in children, but epidemiological evidence of links between fasting and blood lead levels (B-Pb is rare. The purpose of this study was to examine the association between eating a regular breakfast and B-Pb among children using data from the China Jintan Child Cohort Study. Methods Parents completed a questionnaire regarding children's breakfast-eating habit (regular or not, demographics, and food frequency. Whole blood samples were collected from 1,344 children for the measurements of B-Pb and micronutrients (iron, copper, zinc, calcium, and magnesium. B-Pb and other measures were compared between children with and without regular breakfast. Linear regression modeling was used to evaluate the association between regular breakfast and log-transformed B-Pb. The association between regular breakfast and risk of lead poisoning (B-Pb≥10 μg/dL was examined using logistic regression modeling. Results Median B-Pb among children who ate breakfast regularly and those who did not eat breakfast regularly were 6.1 μg/dL and 7.2 μg/dL, respectively. Eating breakfast was also associated with greater zinc blood levels. Adjusting for other relevant factors, the linear regression model revealed that eating breakfast regularly was significantly associated with lower B-Pb (beta = -0.10 units of log-transformed B-Pb compared with children who did not eat breakfast regularly, p = 0.02. Conclusion The present study provides some initial human data supporting the notion that eating a regular breakfast might reduce B-Pb in young children. To our knowledge, this is the first human study exploring the association between breakfast frequency and B-Pb in young children.
Chimeric mitochondrial peptides from contiguous regular and swinger RNA.
Seligmann, Hervé
2016-01-01
Previous mass spectrometry analyses described human mitochondrial peptides entirely translated from swinger RNAs, RNAs where polymerization systematically exchanged nucleotides. Exchanges follow one among 23 bijective transformation rules, nine symmetric exchanges (X ↔ Y, e.g. A ↔ C) and fourteen asymmetric exchanges (X → Y → Z → X, e.g. A → C → G → A), multiplying by 24 DNA's protein coding potential. Abrupt switches from regular to swinger polymerization produce chimeric RNAs. Here, human mitochondrial proteomic analyses assuming abrupt switches between regular and swinger transcriptions, detect chimeric peptides, encoded by part regular, part swinger RNA. Contiguous regular- and swinger-encoded residues within single peptides are stronger evidence for translation of swinger RNA than previously detected, entirely swinger-encoded peptides: regular parts are positive controls matched with contiguous swinger parts, increasing confidence in results. Chimeric peptides are 200 × rarer than swinger peptides (3/100,000 versus 6/1000). Among 186 peptides with > 8 residues for each regular and swinger parts, regular parts of eleven chimeric peptides correspond to six among the thirteen recognized, mitochondrial protein-coding genes. Chimeric peptides matching partly regular proteins are rarer and less expressed than chimeric peptides matching non-coding sequences, suggesting targeted degradation of misfolded proteins. Present results strengthen hypotheses that the short mitogenome encodes far more proteins than hitherto assumed. Entirely swinger-encoded proteins could exist.
Tur\\'an type inequalities for regular Coulomb wave functions
Baricz, Árpád
2015-01-01
Tur\\'an, Mitrinovi\\'c-Adamovi\\'c and Wilker type inequalities are deduced for regular Coulomb wave functions. The proofs are based on a Mittag-Leffler expansion for the regular Coulomb wave function, which may be of independent interest. Moreover, some complete monotonicity results concerning the Coulomb zeta functions and some interlacing properties of the zeros of Coulomb wave functions are given.
Regularization and Complexity Control in Feed-forward Networks
Bishop, C. M.
1995-01-01
In this paper we consider four alternative approaches to complexity control in feed-forward networks based respectively on architecture selection, regularization, early stopping, and training with noise. We show that there are close similarities between these approaches and we argue that, for most practical applications, the technique of regularization should be the method of choice.
Optimal Embeddings of Distance Regular Graphs into Euclidean Spaces
F. Vallentin (Frank)
2008-01-01
htmlabstractIn this paper we give a lower bound for the least distortion embedding of a distance regular graph into Euclidean space. We use the lower bound for finding the least distortion for Hamming graphs, Johnson graphs, and all strongly regular graphs. Our technique involves semidefinite
Degree-regular triangulations of torus and Klein bottle
Indian Academy of Sciences (India)
Home; Journals; Proceedings – Mathematical Sciences; Volume 115; Issue 3 ... A triangulation of a connected closed surface is called degree-regular if each of its vertices have the same degree. ... In [5], Datta and Nilakantan have classified all the degree-regular triangulations of closed surfaces on at most 11 vertices.
Adaptive Regularization of Neural Networks Using Conjugate Gradient
DEFF Research Database (Denmark)
Goutte, Cyril; Larsen, Jan
1998-01-01
Andersen et al. (1997) and Larsen et al. (1996, 1997) suggested a regularization scheme which iteratively adapts regularization parameters by minimizing validation error using simple gradient descent. In this contribution we present an improved algorithm based on the conjugate gradient technique........ Numerical experiments with feedforward neural networks successfully demonstrate improved generalization ability and lower computational cost...
Strictly-regular number system and data structures
DEFF Research Database (Denmark)
Elmasry, Amr Ahmed Abd Elmoneim; Jensen, Claus; Katajainen, Jyrki
2010-01-01
We introduce a new number system that we call the strictly-regular system, which efficiently supports the operations: digit-increment, digit-decrement, cut, concatenate, and add. Compared to other number systems, the strictly-regular system has distinguishable properties. It is superior to the re...
Inclusion Professional Development Model and Regular Middle School Educators
Royster, Otelia; Reglin, Gary L.; Losike-Sedimo, Nonofo
2014-01-01
The purpose of this study was to determine the impact of a professional development model on regular education middle school teachers' knowledge of best practices for teaching inclusive classes and attitudes toward teaching these classes. There were 19 regular education teachers who taught the core subjects. Findings for Research Question 1…
The equivalence problem for LL- and LR-regular grammars
Nijholt, Antinus; Gecsec, F.
It will be shown that the equivalence problem for LL-regular grammars is decidable. Apart from extending the known result for LL(k) grammar equivalence to LLregular grammar equivalence, we obtain an alternative proof of the decidability of LL(k) equivalence. The equivalence prob]em for LL-regular
The Effects of Regular Exercise on the Physical Fitness Levels
Kirandi, Ozlem
2016-01-01
The purpose of the present research is investigating the effects of regular exercise on the physical fitness levels among sedentary individuals. The total of 65 sedentary male individuals between the ages of 19-45, who had never exercises regularly in their lives, participated in the present research. Of these participants, 35 wanted to be…
Regular perturbations in a vector space with indefinite metric
International Nuclear Information System (INIS)
Chiang, C.C.
1975-08-01
The Klein space is discussed in connection with practical applications. Some lemmas are presented which are to be used for the discussion of regular self-adjoint operators. The criteria for the regularity of perturbed operators are given. (U.S.)
Pairing renormalization and regularization within the local density approximation
International Nuclear Information System (INIS)
Borycki, P.J.; Dobaczewski, J.; Nazarewicz, W.; Stoitsov, M.V.
2006-01-01
We discuss methods used in mean-field theories to treat pairing correlations within the local density approximation. Pairing renormalization and regularization procedures are compared in spherical and deformed nuclei. Both prescriptions give fairly similar results, although the theoretical motivation, simplicity, and stability of the regularization procedure make it a method of choice for future applications
Cognitive Aspects of Regularity Exhibit When Neighborhood Disappears
Chen, Sau-Chin; Hu, Jon-Fan
2015-01-01
Although regularity refers to the compatibility between pronunciation of character and sound of phonetic component, it has been suggested as being part of consistency, which is defined by neighborhood characteristics. Two experiments demonstrate how regularity effect is amplified or reduced by neighborhood characteristics and reveals the…
Regularity conditions of the field on a toroidal magnetic surface
International Nuclear Information System (INIS)
Bouligand, M.
1985-06-01
We show that a field B vector which is derived from an analytic canonical potential on an ordinary toroidal surface is regular on this surface when the potential satisfies an elliptic equation (owing to the conservative field) subject to certain conditions of regularity of its coefficients [fr
47 CFR 76.614 - Cable television system regular monitoring.
2010-10-01
...-137 and 225-400 MHz shall provide for a program of regular monitoring for signal leakage by... in these bands of 20 uV/m or greater at a distance of 3 meters. During regular monitoring, any leakage source which produces a field strength of 20 uV/m or greater at a distance of 3 meters in the...
Analysis of regularized Navier-Stokes equations, 2
Ou, Yuh-Roung; Sritharan, S. S.
1989-01-01
A practically important regularization of the Navier-Stokes equations was analyzed. As a continuation of the previous work, the structure of the attractors characterizing the solutins was studied. Local as well as global invariant manifolds were found. Regularity properties of these manifolds are analyzed.
20 CFR 226.33 - Spouse regular annuity rate.
2010-04-01
... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Spouse regular annuity rate. 226.33 Section... COMPUTING EMPLOYEE, SPOUSE, AND DIVORCED SPOUSE ANNUITIES Computing a Spouse or Divorced Spouse Annuity § 226.33 Spouse regular annuity rate. The final tier I and tier II rates, from §§ 226.30 and 226.32, are...
Cui, Miao; Lin, Che-Yi; Su, Yi-Hsien
2017-09-01
Studies on the gene regulatory networks (GRNs) of sea urchin embryos have provided a basic understanding of the molecular mechanisms controlling animal development. The causal links in GRNs have been verified experimentally through perturbation of gene functions. Microinjection of antisense morpholino oligonucleotides (MOs) into the egg is the most widely used approach for gene knockdown in sea urchin embryos. The modification of MOs into a membrane-permeable form (vivo-MOs) has allowed gene knockdown at later developmental stages. Recent advances in genome editing tools, such as zinc-finger nucleases, transcription activator-like effector-based nucleases and the clustered regularly interspaced short palindromic repeat/clustered regularly interspaced short palindromic repeat-associated protein 9 (CRISPR/Cas9) system, have provided methods for gene knockout in sea urchins. Here, we review the use of vivo-MOs and genome editing tools in sea urchin studies since the publication of its genome in 2006. Various applications of the CRISPR/Cas9 system and their potential in studying sea urchin development are also discussed. These new tools will provide more sophisticated experimental methods for studying sea urchin development. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
The genome editing revolution: A CRISPR-Cas TALE off-target story.
Stella, Stefano; Montoya, Guillermo
2016-07-01
In the last 10 years, we have witnessed a blooming of targeted genome editing systems and applications. The area was revolutionized by the discovery and characterization of the transcription activator-like effector proteins, which are easier to engineer to target new DNA sequences than the previously available DNA binding templates, zinc fingers and meganucleases. Recently, the area experimented a quantum leap because of the introduction of the clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein (Cas) system (clustered regularly interspaced short palindromic sequence). This ribonucleoprotein complex protects bacteria from invading DNAs, and it was adapted to be used in genome editing. The CRISPR ribonucleic acid (RNA) molecule guides to the specific DNA site the Cas9 nuclease to cleave the DNA target. Two years and more than 1000 publications later, the CRISPR-Cas system has become the main tool for genome editing in many laboratories. Currently the targeted genome editing technology has been used in many fields and may be a possible approach for human gene therapy. Furthermore, it can also be used to modifying the genomes of model organisms for studying human pathways or to improve key organisms for biotechnological applications, such as plants, livestock genome as well as yeasts and bacterial strains. © 2016 The Authors. BioEssays published by WILEY Periodicals, Inc.
CRISPR technologies for bacterial systems: Current achievements and future directions
DEFF Research Database (Denmark)
Choi, Kyeong Rok; Lee, Sang Yup
2016-01-01
Throughout the decades of its history, the advances in bacteria-based bio-industries have coincided with great leaps in strain engineering technologies. Recently unveiled clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) systems are now revolution......Throughout the decades of its history, the advances in bacteria-based bio-industries have coincided with great leaps in strain engineering technologies. Recently unveiled clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) systems are now...... revolutionizing biotechnology as well as biology. Diverse technologies have been derived from CRISPR/Cas systems in bacteria, yet the applications unfortunately have not been actively employed in bacteria as extensively as in eukaryotic organisms. A recent trend of engineering less explored strains in industrial...... microbiology-metabolic engineering, synthetic biology, and other related disciplines-is demanding facile yet robust tools, and various CRISPR technologies have potential to cater to the demands. Here, we briefly review the science in CRISPR/Cas systems and the milestone inventions that enabled numerous CRISPR...
Consistent Partial Least Squares Path Modeling via Regularization.
Jung, Sunho; Park, JaeHong
2018-01-01
Partial least squares (PLS) path modeling is a component-based structural equation modeling that has been adopted in social and psychological research due to its data-analytic capability and flexibility. A recent methodological advance is consistent PLS (PLSc), designed to produce consistent estimates of path coefficients in structural models involving common factors. In practice, however, PLSc may frequently encounter multicollinearity in part because it takes a strategy of estimating path coefficients based on consistent correlations among independent latent variables. PLSc has yet no remedy for this multicollinearity problem, which can cause loss of statistical power and accuracy in parameter estimation. Thus, a ridge type of regularization is incorporated into PLSc, creating a new technique called regularized PLSc. A comprehensive simulation study is conducted to evaluate the performance of regularized PLSc as compared to its non-regularized counterpart in terms of power and accuracy. The results show that our regularized PLSc is recommended for use when serious multicollinearity is present.
Optimal behaviour can violate the principle of regularity.
Trimmer, Pete C
2013-07-22
Understanding decisions is a fundamental aim of behavioural ecology, psychology and economics. The regularity axiom of utility theory holds that a preference between options should be maintained when other options are made available. Empirical studies have shown that animals violate regularity but this has not been understood from a theoretical perspective, such decisions have therefore been labelled as irrational. Here, I use models of state-dependent behaviour to demonstrate that choices can violate regularity even when behavioural strategies are optimal. I also show that the range of conditions over which regularity should be violated can be larger when options do not always persist into the future. Consequently, utility theory--based on axioms, including transitivity, regularity and the independence of irrelevant alternatives--is undermined, because even alternatives that are never chosen by an animal (in its current state) can be relevant to a decision.
Regularized Regression and Density Estimation based on Optimal Transport
Burger, M.
2012-03-11
The aim of this paper is to investigate a novel nonparametric approach for estimating and smoothing density functions as well as probability densities from discrete samples based on a variational regularization method with the Wasserstein metric as a data fidelity. The approach allows a unified treatment of discrete and continuous probability measures and is hence attractive for various tasks. In particular, the variational model for special regularization functionals yields a natural method for estimating densities and for preserving edges in the case of total variation regularization. In order to compute solutions of the variational problems, a regularized optimal transport problem needs to be solved, for which we discuss several formulations and provide a detailed analysis. Moreover, we compute special self-similar solutions for standard regularization functionals and we discuss several computational approaches and results. © 2012 The Author(s).
Laplacian manifold regularization method for fluorescence molecular tomography
He, Xuelei; Wang, Xiaodong; Yi, Huangjian; Chen, Yanrong; Zhang, Xu; Yu, Jingjing; He, Xiaowei
2017-04-01
Sparse regularization methods have been widely used in fluorescence molecular tomography (FMT) for stable three-dimensional reconstruction. Generally, ℓ1-regularization-based methods allow for utilizing the sparsity nature of the target distribution. However, in addition to sparsity, the spatial structure information should be exploited as well. A joint ℓ1 and Laplacian manifold regularization model is proposed to improve the reconstruction performance, and two algorithms (with and without Barzilai-Borwein strategy) are presented to solve the regularization model. Numerical studies and in vivo experiment demonstrate that the proposed Gradient projection-resolved Laplacian manifold regularization method for the joint model performed better than the comparative algorithm for ℓ1 minimization method in both spatial aggregation and location accuracy.
Three regularities of recognition memory: the role of bias.
Hilford, Andrew; Maloney, Laurence T; Glanzer, Murray; Kim, Kisok
2015-12-01
A basic assumption of Signal Detection Theory is that decisions are made on the basis of likelihood ratios. In a preceding paper, Glanzer, Hilford, and Maloney (Psychonomic Bulletin & Review, 16, 431-455, 2009) showed that the likelihood ratio assumption implies that three regularities will occur in recognition memory: (1) the Mirror Effect, (2) the Variance Effect, (3) the normalized Receiver Operating Characteristic (z-ROC) Length Effect. The paper offered formal proofs and computational demonstrations that decisions based on likelihood ratios produce the three regularities. A survey of data based on group ROCs from 36 studies validated the likelihood ratio assumption by showing that its three implied regularities are ubiquitous. The study noted, however, that bias, another basic factor in Signal Detection Theory, can obscure the Mirror Effect. In this paper we examine how bias affects the regularities at the theoretical level. The theoretical analysis shows: (1) how bias obscures the Mirror Effect, not the other two regularities, and (2) four ways to counter that obscuring. We then report the results of five experiments that support the theoretical analysis. The analyses and the experimental results also demonstrate: (1) that the three regularities govern individual, as well as group, performance, (2) alternative explanations of the regularities are ruled out, and (3) that Signal Detection Theory, correctly applied, gives a simple and unified explanation of recognition memory data.
Learning regularization parameters for general-form Tikhonov
International Nuclear Information System (INIS)
Chung, Julianne; Español, Malena I
2017-01-01
Computing regularization parameters for general-form Tikhonov regularization can be an expensive and difficult task, especially if multiple parameters or many solutions need to be computed in real time. In this work, we assume training data is available and describe an efficient learning approach for computing regularization parameters that can be used for a large set of problems. We consider an empirical Bayes risk minimization framework for finding regularization parameters that minimize average errors for the training data. We first extend methods from Chung et al (2011 SIAM J. Sci. Comput. 33 3132–52) to the general-form Tikhonov problem. Then we develop a learning approach for multi-parameter Tikhonov problems, for the case where all involved matrices are simultaneously diagonalizable. For problems where this is not the case, we describe an approach to compute near-optimal regularization parameters by using operator approximations for the original problem. Finally, we propose a new class of regularizing filters, where solutions correspond to multi-parameter Tikhonov solutions, that requires less data than previously proposed optimal error filters, avoids the generalized SVD, and allows flexibility and novelty in the choice of regularization matrices. Numerical results for 1D and 2D examples using different norms on the errors show the effectiveness of our methods. (paper)
Semisupervised Support Vector Machines With Tangent Space Intrinsic Manifold Regularization.
Sun, Shiliang; Xie, Xijiong
2016-09-01
Semisupervised learning has been an active research topic in machine learning and data mining. One main reason is that labeling examples is expensive and time-consuming, while there are large numbers of unlabeled examples available in many practical problems. So far, Laplacian regularization has been widely used in semisupervised learning. In this paper, we propose a new regularization method called tangent space intrinsic manifold regularization. It is intrinsic to data manifold and favors linear functions on the manifold. Fundamental elements involved in the formulation of the regularization are local tangent space representations, which are estimated by local principal component analysis, and the connections that relate adjacent tangent spaces. Simultaneously, we explore its application to semisupervised classification and propose two new learning algorithms called tangent space intrinsic manifold regularized support vector machines (TiSVMs) and tangent space intrinsic manifold regularized twin SVMs (TiTSVMs). They effectively integrate the tangent space intrinsic manifold regularization consideration. The optimization of TiSVMs can be solved by a standard quadratic programming, while the optimization of TiTSVMs can be solved by a pair of standard quadratic programmings. The experimental results of semisupervised classification problems show the effectiveness of the proposed semisupervised learning algorithms.
Closedness type regularity conditions in convex optimization and beyond
Directory of Open Access Journals (Sweden)
Sorin-Mihai Grad
2016-09-01
Full Text Available The closedness type regularity conditions have proven during the last decade to be viable alternatives to their more restrictive interiority type counterparts, in both convex optimization and different areas where it was successfully applied. In this review article we de- and reconstruct some closedness type regularity conditions formulated by means of epigraphs and subdifferentials, respectively, for general optimization problems in order to stress that they arise naturally when dealing with such problems. The results are then specialized for constrained and unconstrained convex optimization problems. We also hint towards other classes of optimization problems where closedness type regularity conditions were successfully employed and discuss other possible applications of them.
Capped Lp approximations for the composite L0 regularization problem
Li, Qia; Zhang, Na
2017-01-01
The composite L0 function serves as a sparse regularizer in many applications. The algorithmic difficulty caused by the composite L0 regularization (the L0 norm composed with a linear mapping) is usually bypassed through approximating the L0 norm. We consider in this paper capped Lp approximations with $p>0$ for the composite L0 regularization problem. For each $p>0$, the capped Lp function converges to the L0 norm pointwisely as the approximation parameter tends to infinity. We point out tha...
Generalization Performance of Regularized Ranking With Multiscale Kernels.
Zhou, Yicong; Chen, Hong; Lan, Rushi; Pan, Zhibin
2016-05-01
The regularized kernel method for the ranking problem has attracted increasing attentions in machine learning. The previous regularized ranking algorithms are usually based on reproducing kernel Hilbert spaces with a single kernel. In this paper, we go beyond this framework by investigating the generalization performance of the regularized ranking with multiscale kernels. A novel ranking algorithm with multiscale kernels is proposed and its representer theorem is proved. We establish the upper bound of the generalization error in terms of the complexity of hypothesis spaces. It shows that the multiscale ranking algorithm can achieve satisfactory learning rates under mild conditions. Experiments demonstrate the effectiveness of the proposed method for drug discovery and recommendation tasks.
Likelihood ratio decisions in memory: three implied regularities.
Glanzer, Murray; Hilford, Andrew; Maloney, Laurence T
2009-06-01
We analyze four general signal detection models for recognition memory that differ in their distributional assumptions. Our analyses show that a basic assumption of signal detection theory, the likelihood ratio decision axis, implies three regularities in recognition memory: (1) the mirror effect, (2) the variance effect, and (3) the z-ROC length effect. For each model, we present the equations that produce the three regularities and show, in computed examples, how they do so. We then show that the regularities appear in data from a range of recognition studies. The analyses and data in our study support the following generalization: Individuals make efficient recognition decisions on the basis of likelihood ratios.
Fluctuations of quantum fields via zeta function regularization
International Nuclear Information System (INIS)
Cognola, Guido; Zerbini, Sergio; Elizalde, Emilio
2002-01-01
Explicit expressions for the expectation values and the variances of some observables, which are bilinear quantities in the quantum fields on a D-dimensional manifold, are derived making use of zeta function regularization. It is found that the variance, related to the second functional variation of the effective action, requires a further regularization and that the relative regularized variance turns out to be 2/N, where N is the number of the fields, thus being independent of the dimension D. Some illustrating examples are worked through. The issue of the stress tensor is also briefly addressed
Low-Rank Matrix Factorization With Adaptive Graph Regularizer.
Lu, Gui-Fu; Wang, Yong; Zou, Jian
2016-05-01
In this paper, we present a novel low-rank matrix factorization algorithm with adaptive graph regularizer (LMFAGR). We extend the recently proposed low-rank matrix with manifold regularization (MMF) method with an adaptive regularizer. Different from MMF, which constructs an affinity graph in advance, LMFAGR can simultaneously seek graph weight matrix and low-dimensional representations of data. That is, graph construction and low-rank matrix factorization are incorporated into a unified framework, which results in an automatically updated graph rather than a predefined one. The experimental results on some data sets demonstrate that the proposed algorithm outperforms the state-of-the-art low-rank matrix factorization methods.
Regularization theory for ill-posed problems selected topics
Lu, Shuai
2013-01-01
Thismonograph is a valuable contribution to thehighly topical and extremly productive field ofregularisationmethods for inverse and ill-posed problems. The author is an internationally outstanding and acceptedmathematicianin this field. In his book he offers a well-balanced mixtureof basic and innovative aspects.He demonstrates new,differentiatedviewpoints, and important examples for applications. The bookdemontrates thecurrent developments inthe field of regularization theory,such as multiparameter regularization and regularization in learning theory. The book is written for graduate and PhDs
On the theory of drainage area for regular and non-regular points
Bonetti, S.; Bragg, A. D.; Porporato, A.
2018-03-01
The drainage area is an important, non-local property of a landscape, which controls surface and subsurface hydrological fluxes. Its role in numerous ecohydrological and geomorphological applications has given rise to several numerical methods for its computation. However, its theoretical analysis has lagged behind. Only recently, an analytical definition for the specific catchment area was proposed (Gallant & Hutchinson. 2011 Water Resour. Res. 47, W05535. (doi:10.1029/2009WR008540)), with the derivation of a differential equation whose validity is limited to regular points of the watershed. Here, we show that such a differential equation can be derived from a continuity equation (Chen et al. 2014 Geomorphology 219, 68-86. (doi:10.1016/j.geomorph.2014.04.037)) and extend the theory to critical and singular points both by applying Gauss's theorem and by means of a dynamical systems approach to define basins of attraction of local surface minima. Simple analytical examples as well as applications to more complex topographic surfaces are examined. The theoretical description of topographic features and properties, such as the drainage area, channel lines and watershed divides, can be broadly adopted to develop and test the numerical algorithms currently used in digital terrain analysis for the computation of the drainage area, as well as for the theoretical analysis of landscape evolution and stability.
Automatic Constraint Detection for 2D Layout Regularization.
Jiang, Haiyong; Nan, Liangliang; Yan, Dong-Ming; Dong, Weiming; Zhang, Xiaopeng; Wonka, Peter
2016-08-01
In this paper, we address the problem of constraint detection for layout regularization. The layout we consider is a set of two-dimensional elements where each element is represented by its bounding box. Layout regularization is important in digitizing plans or images, such as floor plans and facade images, and in the improvement of user-created contents, such as architectural drawings and slide layouts. To regularize a layout, we aim to improve the input by detecting and subsequently enforcing alignment, size, and distance constraints between layout elements. Similar to previous work, we formulate layout regularization as a quadratic programming problem. In addition, we propose a novel optimization algorithm that automatically detects constraints. We evaluate the proposed framework using a variety of input layouts from different applications. Our results demonstrate that our method has superior performance to the state of the art.
Regularized multivariate regression models with skew-t error distributions
Chen, Lianfu; Pourahmadi, Mohsen; Maadooliat, Mehdi
2014-01-01
We consider regularization of the parameters in multivariate linear regression models with the errors having a multivariate skew-t distribution. An iterative penalized likelihood procedure is proposed for constructing sparse estimators of both
A Regularized Algorithm for the Proximal Split Feasibility Problem
Directory of Open Access Journals (Sweden)
Zhangsong Yao
2014-01-01
Full Text Available The proximal split feasibility problem has been studied. A regularized method has been presented for solving the proximal split feasibility problem. Strong convergence theorem is given.
Anaemia in Patients with Diabetes Mellitus attending regular ...
African Journals Online (AJOL)
Anaemia in Patients with Diabetes Mellitus attending regular Diabetic ... Nigerian Journal of Health and Biomedical Sciences ... some patients may omit important food items in their daily diet for fear of increasing their blood sugar level.
Automatic Constraint Detection for 2D Layout Regularization
Jiang, Haiyong
2015-09-18
In this paper, we address the problem of constraint detection for layout regularization. As layout we consider a set of two-dimensional elements where each element is represented by its bounding box. Layout regularization is important for digitizing plans or images, such as floor plans and facade images, and for the improvement of user created contents, such as architectural drawings and slide layouts. To regularize a layout, we aim to improve the input by detecting and subsequently enforcing alignment, size, and distance constraints between layout elements. Similar to previous work, we formulate the layout regularization as a quadratic programming problem. In addition, we propose a novel optimization algorithm to automatically detect constraints. In our results, we evaluate the proposed framework on a variety of input layouts from different applications, which demonstrates our method has superior performance to the state of the art.
Body composition, disordered eating and menstrual regularity in a ...
African Journals Online (AJOL)
Body composition, disordered eating and menstrual regularity in a group of South African ... e between body composition and disordered eating in irregular vs normal menstruating athletes. ... measured by air displacement plethysmography.
A new approach to nonlinear constrained Tikhonov regularization
Ito, Kazufumi; Jin, Bangti
2011-01-01
operator. The approach is exploited to derive convergence rate results for a priori as well as a posteriori choice rules, e.g., discrepancy principle and balancing principle, for selecting the regularization parameter. The idea is further illustrated on a
Supporting primary school teachers in differentiating in the regular classroom
Eysink, Tessa H.S.; Hulsbeek, Manon; Gijlers, Hannie
Many primary school teachers experience difficulties in effectively differentiating in the regular classroom. This study investigated the effect of the STIP-approach on teachers' differentiation activities and self-efficacy, and children's learning outcomes and instructional value. Teachers using
Lavrentiev regularization method for nonlinear ill-posed problems
International Nuclear Information System (INIS)
Kinh, Nguyen Van
2002-10-01
In this paper we shall be concerned with Lavientiev regularization method to reconstruct solutions x 0 of non ill-posed problems F(x)=y o , where instead of y 0 noisy data y δ is an element of X with absolut(y δ -y 0 ) ≤ δ are given and F:X→X is an accretive nonlinear operator from a real reflexive Banach space X into itself. In this regularization method solutions x α δ are obtained by solving the singularly perturbed nonlinear operator equation F(x)+α(x-x*)=y δ with some initial guess x*. Assuming certain conditions concerning the operator F and the smoothness of the element x*-x 0 we derive stability estimates which show that the accuracy of the regularized solutions is order optimal provided that the regularization parameter α has been chosen properly. (author)
Regularized plane-wave least-squares Kirchhoff migration
Wang, Xin; Dai, Wei; Schuster, Gerard T.
2013-01-01
A Kirchhoff least-squares migration (LSM) is developed in the prestack plane-wave domain to increase the quality of migration images. A regularization term is included that accounts for mispositioning of reflectors due to errors in the velocity
Automatic Constraint Detection for 2D Layout Regularization
Jiang, Haiyong; Nan, Liangliang; Yan, Dongming; Dong, Weiming; Zhang, Xiaopeng; Wonka, Peter
2015-01-01
plans or images, such as floor plans and facade images, and for the improvement of user created contents, such as architectural drawings and slide layouts. To regularize a layout, we aim to improve the input by detecting and subsequently enforcing
Regularization method for solving the inverse scattering problem
International Nuclear Information System (INIS)
Denisov, A.M.; Krylov, A.S.
1985-01-01
The inverse scattering problem for the Schroedinger radial equation consisting in determining the potential according to the scattering phase is considered. The problem of potential restoration according to the phase specified with fixed error in a finite range is solved by the regularization method based on minimization of the Tikhonov's smoothing functional. The regularization method is used for solving the problem of neutron-proton potential restoration according to the scattering phases. The determined potentials are given in the table
Viscous Regularization of the Euler Equations and Entropy Principles
Guermond, Jean-Luc
2014-03-11
This paper investigates a general class of viscous regularizations of the compressible Euler equations. A unique regularization is identified that is compatible with all the generalized entropies, à la [Harten et al., SIAM J. Numer. Anal., 35 (1998), pp. 2117-2127], and satisfies the minimum entropy principle. A connection with a recently proposed phenomenological model by [H. Brenner, Phys. A, 370 (2006), pp. 190-224] is made. © 2014 Society for Industrial and Applied Mathematics.
Dimensional versus lattice regularization within Luescher's Yang Mills theory
International Nuclear Information System (INIS)
Diekmann, B.; Langer, M.; Schuette, D.
1993-01-01
It is pointed out that the coefficients of Luescher's effective model space Hamiltonian, which is based upon dimensional regularization techniques, can be reproduced by applying folded diagram perturbation theory to the Kogut Susskind Hamiltonian and by performing a lattice continuum limit (keeping the volume fixed). Alternative cutoff regularizations of the Hamiltonian are in general inconsistent, the critical point beeing the correct prediction for Luescher's tadpole coefficient which is formally quadratically divergent and which has to become a well defined (negative) number. (orig.)
Left regular bands of groups of left quotients
International Nuclear Information System (INIS)
El-Qallali, A.
1988-10-01
A semigroup S which has a left regular band of groups as a semigroup of left quotients is shown to be the semigroup which is a left regular band of right reversible cancellative semigroups. An alternative characterization is provided by using spinned products. These results are applied to the case where S is a superabundant whose set of idempotents forms a left normal band. (author). 13 refs
Human visual system automatically encodes sequential regularities of discrete events.
Kimura, Motohiro; Schröger, Erich; Czigler, István; Ohira, Hideki
2010-06-01
For our adaptive behavior in a dynamically changing environment, an essential task of the brain is to automatically encode sequential regularities inherent in the environment into a memory representation. Recent studies in neuroscience have suggested that sequential regularities embedded in discrete sensory events are automatically encoded into a memory representation at the level of the sensory system. This notion is largely supported by evidence from investigations using auditory mismatch negativity (auditory MMN), an event-related brain potential (ERP) correlate of an automatic memory-mismatch process in the auditory sensory system. However, it is still largely unclear whether or not this notion can be generalized to other sensory modalities. The purpose of the present study was to investigate the contribution of the visual sensory system to the automatic encoding of sequential regularities using visual mismatch negativity (visual MMN), an ERP correlate of an automatic memory-mismatch process in the visual sensory system. To this end, we conducted a sequential analysis of visual MMN in an oddball sequence consisting of infrequent deviant and frequent standard stimuli, and tested whether the underlying memory representation of visual MMN generation contains only a sensory memory trace of standard stimuli (trace-mismatch hypothesis) or whether it also contains sequential regularities extracted from the repetitive standard sequence (regularity-violation hypothesis). The results showed that visual MMN was elicited by first deviant (deviant stimuli following at least one standard stimulus), second deviant (deviant stimuli immediately following first deviant), and first standard (standard stimuli immediately following first deviant), but not by second standard (standard stimuli immediately following first standard). These results are consistent with the regularity-violation hypothesis, suggesting that the visual sensory system automatically encodes sequential
Estimation of the global regularity of a multifractional Brownian motion
DEFF Research Database (Denmark)
Lebovits, Joachim; Podolskij, Mark
This paper presents a new estimator of the global regularity index of a multifractional Brownian motion. Our estimation method is based upon a ratio statistic, which compares the realized global quadratic variation of a multifractional Brownian motion at two different frequencies. We show that a ...... that a logarithmic transformation of this statistic converges in probability to the minimum of the Hurst functional parameter, which is, under weak assumptions, identical to the global regularity index of the path....
Regularization of the quantum field theory of charges and monopoles
International Nuclear Information System (INIS)
Panagiotakopoulos, C.
1981-09-01
A gauge invariant regularization procedure for quantum field theories of electric and magnetic charges based on Zwanziger's local formulation is proposed. The bare regularized full Green's functions of gauge invariant operators are shown to be Lorentz invariant. This would have as a consequence the Lorentz invariance of the finite Green's functions that might result after any reasonable subtraction if such a subtraction can be found. (author)
Borderline personality disorder and regularly drinking alcohol before sex.
Thompson, Ronald G; Eaton, Nicholas R; Hu, Mei-Chen; Hasin, Deborah S
2017-07-01
Drinking alcohol before sex increases the likelihood of engaging in unprotected intercourse, having multiple sexual partners and becoming infected with sexually transmitted infections. Borderline personality disorder (BPD), a complex psychiatric disorder characterised by pervasive instability in emotional regulation, self-image, interpersonal relationships and impulse control, is associated with substance use disorders and sexual risk behaviours. However, no study has examined the relationship between BPD and drinking alcohol before sex in the USA. This study examined the association between BPD and regularly drinking before sex in a nationally representative adult sample. Participants were 17 491 sexually active drinkers from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Logistic regression models estimated effects of BPD diagnosis, specific borderline diagnostic criteria and BPD criterion count on the likelihood of regularly (mostly or always) drinking alcohol before sex, adjusted for controls. Borderline personality disorder diagnosis doubled the odds of regularly drinking before sex [adjusted odds ratio (AOR) = 2.26; confidence interval (CI) = 1.63, 3.14]. Of nine diagnostic criteria, impulsivity in areas that are self-damaging remained a significant predictor of regularly drinking before sex (AOR = 1.82; CI = 1.42, 2.35). The odds of regularly drinking before sex increased by 20% for each endorsed criterion (AOR = 1.20; CI = 1.14, 1.27) DISCUSSION AND CONCLUSIONS: This is the first study to examine the relationship between BPD and regularly drinking alcohol before sex in the USA. Substance misuse treatment should assess regularly drinking before sex, particularly among patients with BPD, and BPD treatment should assess risk at the intersection of impulsivity, sexual behaviour and substance use. [Thompson Jr RG, Eaton NR, Hu M-C, Hasin DS Borderline personality disorder and regularly drinking alcohol
The Impact of Computerization on Regular Employment (Japanese)
SUNADA Mitsuru; HIGUCHI Yoshio; ABE Masahiro
2004-01-01
This paper uses micro data from the Basic Survey of Japanese Business Structure and Activity to analyze the effects of companies' introduction of information and telecommunications technology on employment structures, especially regular versus non-regular employment. Firstly, examination of trends in the ratio of part-time workers recorded in the Basic Survey shows that part-time worker ratios in manufacturing firms are rising slightly, but that companies with a high proportion of part-timers...
Analytic regularization of the Yukawa model at finite temperature
International Nuclear Information System (INIS)
Malbouisson, A.P.C.; Svaiter, N.F.; Svaiter, B.F.
1996-07-01
It is analysed the one-loop fermionic contribution for the scalar effective potential in the temperature dependent Yukawa model. Ir order to regularize the model a mix between dimensional and analytic regularization procedures is used. It is found a general expression for the fermionic contribution in arbitrary spacetime dimension. It is also found that in D = 3 this contribution is finite. (author). 19 refs
The relationship between lifestyle regularity and subjective sleep quality
Monk, Timothy H.; Reynolds, Charles F 3rd; Buysse, Daniel J.; DeGrazia, Jean M.; Kupfer, David J.
2003-01-01
In previous work we have developed a diary instrument-the Social Rhythm Metric (SRM), which allows the assessment of lifestyle regularity-and a questionnaire instrument--the Pittsburgh Sleep Quality Index (PSQI), which allows the assessment of subjective sleep quality. The aim of the present study was to explore the relationship between lifestyle regularity and subjective sleep quality. Lifestyle regularity was assessed by both standard (SRM-17) and shortened (SRM-5) metrics; subjective sleep quality was assessed by the PSQI. We hypothesized that high lifestyle regularity would be conducive to better sleep. Both instruments were given to a sample of 100 healthy subjects who were studied as part of a variety of different experiments spanning a 9-yr time frame. Ages ranged from 19 to 49 yr (mean age: 31.2 yr, s.d.: 7.8 yr); there were 48 women and 52 men. SRM scores were derived from a two-week diary. The hypothesis was confirmed. There was a significant (rho = -0.4, p subjects with higher levels of lifestyle regularity reported fewer sleep problems. This relationship was also supported by a categorical analysis, where the proportion of "poor sleepers" was doubled in the "irregular types" group as compared with the "non-irregular types" group. Thus, there appears to be an association between lifestyle regularity and good sleep, though the direction of causality remains to be tested.
Regularity criteria for incompressible magnetohydrodynamics equations in three dimensions
International Nuclear Information System (INIS)
Lin, Hongxia; Du, Lili
2013-01-01
In this paper, we give some new global regularity criteria for three-dimensional incompressible magnetohydrodynamics (MHD) equations. More precisely, we provide some sufficient conditions in terms of the derivatives of the velocity or pressure, for the global regularity of strong solutions to 3D incompressible MHD equations in the whole space, as well as for periodic boundary conditions. Moreover, the regularity criterion involving three of the nine components of the velocity gradient tensor is also obtained. The main results generalize the recent work by Cao and Wu (2010 Two regularity criteria for the 3D MHD equations J. Diff. Eqns 248 2263–74) and the analysis in part is based on the works by Cao C and Titi E (2008 Regularity criteria for the three-dimensional Navier–Stokes equations Indiana Univ. Math. J. 57 2643–61; 2011 Gobal regularity criterion for the 3D Navier–Stokes equations involving one entry of the velocity gradient tensor Arch. Rational Mech. Anal. 202 919–32) for 3D incompressible Navier–Stokes equations. (paper)
Geostatistical regularization operators for geophysical inverse problems on irregular meshes
Jordi, C.; Doetsch, J.; Günther, T.; Schmelzbach, C.; Robertsson, J. OA
2018-05-01
Irregular meshes allow to include complicated subsurface structures into geophysical modelling and inverse problems. The non-uniqueness of these inverse problems requires appropriate regularization that can incorporate a priori information. However, defining regularization operators for irregular discretizations is not trivial. Different schemes for calculating smoothness operators on irregular meshes have been proposed. In contrast to classical regularization constraints that are only defined using the nearest neighbours of a cell, geostatistical operators include a larger neighbourhood around a particular cell. A correlation model defines the extent of the neighbourhood and allows to incorporate information about geological structures. We propose an approach to calculate geostatistical operators for inverse problems on irregular meshes by eigendecomposition of a covariance matrix that contains the a priori geological information. Using our approach, the calculation of the operator matrix becomes tractable for 3-D inverse problems on irregular meshes. We tested the performance of the geostatistical regularization operators and compared them against the results of anisotropic smoothing in inversions of 2-D surface synthetic electrical resistivity tomography (ERT) data as well as in the inversion of a realistic 3-D cross-well synthetic ERT scenario. The inversions of 2-D ERT and seismic traveltime field data with geostatistical regularization provide results that are in good accordance with the expected geology and thus facilitate their interpretation. In particular, for layered structures the geostatistical regularization provides geologically more plausible results compared to the anisotropic smoothness constraints.
Bounded Perturbation Regularization for Linear Least Squares Estimation
Ballal, Tarig
2017-10-18
This paper addresses the problem of selecting the regularization parameter for linear least-squares estimation. We propose a new technique called bounded perturbation regularization (BPR). In the proposed BPR method, a perturbation with a bounded norm is allowed into the linear transformation matrix to improve the singular-value structure. Following this, the problem is formulated as a min-max optimization problem. Next, the min-max problem is converted to an equivalent minimization problem to estimate the unknown vector quantity. The solution of the minimization problem is shown to converge to that of the ℓ2 -regularized least squares problem, with the unknown regularizer related to the norm bound of the introduced perturbation through a nonlinear constraint. A procedure is proposed that combines the constraint equation with the mean squared error (MSE) criterion to develop an approximately optimal regularization parameter selection algorithm. Both direct and indirect applications of the proposed method are considered. Comparisons with different Tikhonov regularization parameter selection methods, as well as with other relevant methods, are carried out. Numerical results demonstrate that the proposed method provides significant improvement over state-of-the-art methods.
Near-Regular Structure Discovery Using Linear Programming
Huang, Qixing
2014-06-02
Near-regular structures are common in manmade and natural objects. Algorithmic detection of such regularity greatly facilitates our understanding of shape structures, leads to compact encoding of input geometries, and enables efficient generation and manipulation of complex patterns on both acquired and synthesized objects. Such regularity manifests itself both in the repetition of certain geometric elements, as well as in the structured arrangement of the elements. We cast the regularity detection problem as an optimization and efficiently solve it using linear programming techniques. Our optimization has a discrete aspect, that is, the connectivity relationships among the elements, as well as a continuous aspect, namely the locations of the elements of interest. Both these aspects are captured by our near-regular structure extraction framework, which alternates between discrete and continuous optimizations. We demonstrate the effectiveness of our framework on a variety of problems including near-regular structure extraction, structure-preserving pattern manipulation, and markerless correspondence detection. Robustness results with respect to geometric and topological noise are presented on synthesized, real-world, and also benchmark datasets. © 2014 ACM.
An adaptive regularization parameter choice strategy for multispectral bioluminescence tomography
Energy Technology Data Exchange (ETDEWEB)
Feng Jinchao; Qin Chenghu; Jia Kebin; Han Dong; Liu Kai; Zhu Shouping; Yang Xin; Tian Jie [Medical Image Processing Group, Institute of Automation, Chinese Academy of Sciences, P. O. Box 2728, Beijing 100190 (China); College of Electronic Information and Control Engineering, Beijing University of Technology, Beijing 100124 (China); Medical Image Processing Group, Institute of Automation, Chinese Academy of Sciences, P. O. Box 2728, Beijing 100190 (China); Medical Image Processing Group, Institute of Automation, Chinese Academy of Sciences, P. O. Box 2728, Beijing 100190 (China) and School of Life Sciences and Technology, Xidian University, Xi' an 710071 (China)
2011-11-15
Purpose: Bioluminescence tomography (BLT) provides an effective tool for monitoring physiological and pathological activities in vivo. However, the measured data in bioluminescence imaging are corrupted by noise. Therefore, regularization methods are commonly used to find a regularized solution. Nevertheless, for the quality of the reconstructed bioluminescent source obtained by regularization methods, the choice of the regularization parameters is crucial. To date, the selection of regularization parameters remains challenging. With regards to the above problems, the authors proposed a BLT reconstruction algorithm with an adaptive parameter choice rule. Methods: The proposed reconstruction algorithm uses a diffusion equation for modeling the bioluminescent photon transport. The diffusion equation is solved with a finite element method. Computed tomography (CT) images provide anatomical information regarding the geometry of the small animal and its internal organs. To reduce the ill-posedness of BLT, spectral information and the optimal permissible source region are employed. Then, the relationship between the unknown source distribution and multiview and multispectral boundary measurements is established based on the finite element method and the optimal permissible source region. Since the measured data are noisy, the BLT reconstruction is formulated as l{sub 2} data fidelity and a general regularization term. When choosing the regularization parameters for BLT, an efficient model function approach is proposed, which does not require knowledge of the noise level. This approach only requests the computation of the residual and regularized solution norm. With this knowledge, we construct the model function to approximate the objective function, and the regularization parameter is updated iteratively. Results: First, the micro-CT based mouse phantom was used for simulation verification. Simulation experiments were used to illustrate why multispectral data were used
The neural substrates of impaired finger tapping regularity after stroke.
Calautti, Cinzia; Jones, P Simon; Guincestre, Jean-Yves; Naccarato, Marcello; Sharma, Nikhil; Day, Diana J; Carpenter, T Adrian; Warburton, Elizabeth A; Baron, Jean-Claude
2010-03-01
Not only finger tapping speed, but also tapping regularity can be impaired after stroke, contributing to reduced dexterity. The neural substrates of impaired tapping regularity after stroke are unknown. Previous work suggests damage to the dorsal premotor cortex (PMd) and prefrontal cortex (PFCx) affects externally-cued hand movement. We tested the hypothesis that these two areas are involved in impaired post-stroke tapping regularity. In 19 right-handed patients (15 men/4 women; age 45-80 years; purely subcortical in 16) partially to fully recovered from hemiparetic stroke, tri-axial accelerometric quantitative assessment of tapping regularity and BOLD fMRI were obtained during fixed-rate auditory-cued index-thumb tapping, in a single session 10-230 days after stroke. A strong random-effect correlation between tapping regularity index and fMRI signal was found in contralesional PMd such that the worse the regularity the stronger the activation. A significant correlation in the opposite direction was also present within contralesional PFCx. Both correlations were maintained if maximal index tapping speed, degree of paresis and time since stroke were added as potential confounds. Thus, the contralesional PMd and PFCx appear to be involved in the impaired ability of stroke patients to fingertap in pace with external cues. The findings for PMd are consistent with repetitive TMS investigations in stroke suggesting a role for this area in affected-hand movement timing. The inverse relationship with tapping regularity observed for the PFCx and the PMd suggests these two anatomically-connected areas negatively co-operate. These findings have implications for understanding the disruption and reorganization of the motor systems after stroke. Copyright (c) 2009 Elsevier Inc. All rights reserved.
Reducing errors in the GRACE gravity solutions using regularization
Save, Himanshu; Bettadpur, Srinivas; Tapley, Byron D.
2012-09-01
The nature of the gravity field inverse problem amplifies the noise in the GRACE data, which creeps into the mid and high degree and order harmonic coefficients of the Earth's monthly gravity fields provided by GRACE. Due to the use of imperfect background models and data noise, these errors are manifested as north-south striping in the monthly global maps of equivalent water heights. In order to reduce these errors, this study investigates the use of the L-curve method with Tikhonov regularization. L-curve is a popular aid for determining a suitable value of the regularization parameter when solving linear discrete ill-posed problems using Tikhonov regularization. However, the computational effort required to determine the L-curve is prohibitively high for a large-scale problem like GRACE. This study implements a parameter-choice method, using Lanczos bidiagonalization which is a computationally inexpensive approximation to L-curve. Lanczos bidiagonalization is implemented with orthogonal transformation in a parallel computing environment and projects a large estimation problem on a problem of the size of about 2 orders of magnitude smaller for computing the regularization parameter. Errors in the GRACE solution time series have certain characteristics that vary depending on the ground track coverage of the solutions. These errors increase with increasing degree and order. In addition, certain resonant and near-resonant harmonic coefficients have higher errors as compared with the other coefficients. Using the knowledge of these characteristics, this study designs a regularization matrix that provides a constraint on the geopotential coefficients as a function of its degree and order. This regularization matrix is then used to compute the appropriate regularization parameter for each monthly solution. A 7-year time-series of the candidate regularized solutions (Mar 2003-Feb 2010) show markedly reduced error stripes compared with the unconstrained GRACE release 4
Rotating Hayward’s regular black hole as particle accelerator
International Nuclear Information System (INIS)
Amir, Muhammed; Ghosh, Sushant G.
2015-01-01
Recently, Bañados, Silk and West (BSW) demonstrated that the extremal Kerr black hole can act as a particle accelerator with arbitrarily high center-of-mass energy (E CM ) when the collision takes place near the horizon. The rotating Hayward’s regular black hole, apart from Mass (M) and angular momentum (a), has a new parameter g (g>0 is a constant) that provides a deviation from the Kerr black hole. We demonstrate that for each g, with M=1, there exist critical a E and r H E , which corresponds to a regular extremal black hole with degenerate horizons, and a E decreases whereas r H E increases with increase in g. While aregular non-extremal black hole with outer and inner horizons. We apply the BSW process to the rotating Hayward’s regular black hole, for different g, and demonstrate numerically that the E CM diverges in the vicinity of the horizon for the extremal cases thereby suggesting that a rotating regular black hole can also act as a particle accelerator and thus in turn provide a suitable framework for Plank-scale physics. For a non-extremal case, there always exist a finite upper bound for the E CM , which increases with the deviation parameter g.
Consistent Partial Least Squares Path Modeling via Regularization
Directory of Open Access Journals (Sweden)
Sunho Jung
2018-02-01
Full Text Available Partial least squares (PLS path modeling is a component-based structural equation modeling that has been adopted in social and psychological research due to its data-analytic capability and flexibility. A recent methodological advance is consistent PLS (PLSc, designed to produce consistent estimates of path coefficients in structural models involving common factors. In practice, however, PLSc may frequently encounter multicollinearity in part because it takes a strategy of estimating path coefficients based on consistent correlations among independent latent variables. PLSc has yet no remedy for this multicollinearity problem, which can cause loss of statistical power and accuracy in parameter estimation. Thus, a ridge type of regularization is incorporated into PLSc, creating a new technique called regularized PLSc. A comprehensive simulation study is conducted to evaluate the performance of regularized PLSc as compared to its non-regularized counterpart in terms of power and accuracy. The results show that our regularized PLSc is recommended for use when serious multicollinearity is present.
Method of transferring regular shaped vessel into cell
International Nuclear Information System (INIS)
Murai, Tsunehiko.
1997-01-01
The present invention concerns a method of transferring regular shaped vessels from a non-contaminated area to a contaminated cell. A passage hole for allowing the regular shaped vessels to pass in the longitudinal direction is formed to a partitioning wall at the bottom of the contaminated cell. A plurality of regular shaped vessel are stacked in multiple stages in a vertical direction from the non-contaminated area present below the passage hole, allowed to pass while being urged and transferred successively into the contaminated cell. As a result, since they are transferred while substantially closing the passage hole by the regular shaped vessels, radiation rays or contaminated materials are prevented from discharging from the contaminated cell to the non-contaminated area. Since there is no requirement to open/close an isolation door frequently, the workability upon transfer can be improved remarkably. In addition, the sealing member for sealing the gap between the regular shaped vessel passing through the passage hole and the partitioning wall of the bottom is disposed to the passage hole, the contaminated materials in the contaminated cells can be prevented from discharging from the gap to the non-contaminated area. (N.H.)
X-ray computed tomography using curvelet sparse regularization.
Wieczorek, Matthias; Frikel, Jürgen; Vogel, Jakob; Eggl, Elena; Kopp, Felix; Noël, Peter B; Pfeiffer, Franz; Demaret, Laurent; Lasser, Tobias
2015-04-01
Reconstruction of x-ray computed tomography (CT) data remains a mathematically challenging problem in medical imaging. Complementing the standard analytical reconstruction methods, sparse regularization is growing in importance, as it allows inclusion of prior knowledge. The paper presents a method for sparse regularization based on the curvelet frame for the application to iterative reconstruction in x-ray computed tomography. In this work, the authors present an iterative reconstruction approach based on the alternating direction method of multipliers using curvelet sparse regularization. Evaluation of the method is performed on a specifically crafted numerical phantom dataset to highlight the method's strengths. Additional evaluation is performed on two real datasets from commercial scanners with different noise characteristics, a clinical bone sample acquired in a micro-CT and a human abdomen scanned in a diagnostic CT. The results clearly illustrate that curvelet sparse regularization has characteristic strengths. In particular, it improves the restoration and resolution of highly directional, high contrast features with smooth contrast variations. The authors also compare this approach to the popular technique of total variation and to traditional filtered backprojection. The authors conclude that curvelet sparse regularization is able to improve reconstruction quality by reducing noise while preserving highly directional features.
On the MSE Performance and Optimization of Regularized Problems
Alrashdi, Ayed
2016-11-01
The amount of data that has been measured, transmitted/received, and stored in the recent years has dramatically increased. So, today, we are in the world of big data. Fortunately, in many applications, we can take advantages of possible structures and patterns in the data to overcome the curse of dimensionality. The most well known structures include sparsity, low-rankness, block sparsity. This includes a wide range of applications such as machine learning, medical imaging, signal processing, social networks and computer vision. This also led to a specific interest in recovering signals from noisy compressed measurements (Compressed Sensing (CS) problem). Such problems are generally ill-posed unless the signal is structured. The structure can be captured by a regularizer function. This gives rise to a potential interest in regularized inverse problems, where the process of reconstructing the structured signal can be modeled as a regularized problem. This thesis particularly focuses on finding the optimal regularization parameter for such problems, such as ridge regression, LASSO, square-root LASSO and low-rank Generalized LASSO. Our goal is to optimally tune the regularizer to minimize the mean-squared error (MSE) of the solution when the noise variance or structure parameters are unknown. The analysis is based on the framework of the Convex Gaussian Min-max Theorem (CGMT) that has been used recently to precisely predict performance errors.
Ice crystal interspacing in frozen foods
Sman, van der R.G.M.; Voda, A.; Dalen, van G.; Duijster, A.
2013-01-01
In this paper we show that the ice crystal growth in food and biomaterials is a function of the freezing rate. Our experimental data and literature data on other biomaterials collapse to a single curve, if plotted against the freezing rate. The fitted correlation is compared to scaling rules
The relationship between synchronization and percolation for regular networks
Li, Zhe; Ren, Tao; Xu, Yanjie; Jin, Jianyu
2018-02-01
Synchronization and percolation are two essential phenomena in complex dynamical networks. They have been studied widely, but previously treated as unrelated. In this paper, the relationship between synchronization and percolation are revealed for regular networks. Firstly, we discovered a bridge between synchronization and percolation by using the eigenvalues of the Laplacian matrix to describe the synchronizability and using the eigenvalues of the adjacency matrix to describe the percolation threshold. Then, we proposed a method to find the relationship for regular networks based on the topology of networks. Particularly, if the degree distribution of the network is subject to delta function, we show that only the eigenvalues of the adjacency matrix need to be calculated. Finally, several examples are provided to demonstrate how to apply our proposed method to discover the relationship between synchronization and percolation for regular networks.
Variational analysis of regular mappings theory and applications
Ioffe, Alexander D
2017-01-01
This monograph offers the first systematic account of (metric) regularity theory in variational analysis. It presents new developments alongside classical results and demonstrates the power of the theory through applications to various problems in analysis and optimization theory. The origins of metric regularity theory can be traced back to a series of fundamental ideas and results of nonlinear functional analysis and global analysis centered around problems of existence and stability of solutions of nonlinear equations. In variational analysis, regularity theory goes far beyond the classical setting and is also concerned with non-differentiable and multi-valued operators. The present volume explores all basic aspects of the theory, from the most general problems for mappings between metric spaces to those connected with fairly concrete and important classes of operators acting in Banach and finite dimensional spaces. Written by a leading expert in the field, the book covers new and powerful techniques, whic...
Variational regularization of 3D data experiments with Matlab
Montegranario, Hebert
2014-01-01
Variational Regularization of 3D Data provides an introduction to variational methods for data modelling and its application in computer vision. In this book, the authors identify interpolation as an inverse problem that can be solved by Tikhonov regularization. The proposed solutions are generalizations of one-dimensional splines, applicable to n-dimensional data and the central idea is that these splines can be obtained by regularization theory using a trade-off between the fidelity of the data and smoothness properties.As a foundation, the authors present a comprehensive guide to the necessary fundamentals of functional analysis and variational calculus, as well as splines. The implementation and numerical experiments are illustrated using MATLAB®. The book also includes the necessary theoretical background for approximation methods and some details of the computer implementation of the algorithms. A working knowledge of multivariable calculus and basic vector and matrix methods should serve as an adequat...
Wavelet domain image restoration with adaptive edge-preserving regularization.
Belge, M; Kilmer, M E; Miller, E L
2000-01-01
In this paper, we consider a wavelet based edge-preserving regularization scheme for use in linear image restoration problems. Our efforts build on a collection of mathematical results indicating that wavelets are especially useful for representing functions that contain discontinuities (i.e., edges in two dimensions or jumps in one dimension). We interpret the resulting theory in a statistical signal processing framework and obtain a highly flexible framework for adapting the degree of regularization to the local structure of the underlying image. In particular, we are able to adapt quite easily to scale-varying and orientation-varying features in the image while simultaneously retaining the edge preservation properties of the regularizer. We demonstrate a half-quadratic algorithm for obtaining the restorations from observed data.
Breast ultrasound tomography with total-variation regularization
Energy Technology Data Exchange (ETDEWEB)
Huang, Lianjie [Los Alamos National Laboratory; Li, Cuiping [KARMANOS CANCER INSTIT.; Duric, Neb [KARMANOS CANCER INSTIT
2009-01-01
Breast ultrasound tomography is a rapidly developing imaging modality that has the potential to impact breast cancer screening and diagnosis. A new ultrasound breast imaging device (CURE) with a ring array of transducers has been designed and built at Karmanos Cancer Institute, which acquires both reflection and transmission ultrasound signals. To extract the sound-speed information from the breast data acquired by CURE, we have developed an iterative sound-speed image reconstruction algorithm for breast ultrasound transmission tomography based on total-variation (TV) minimization. We investigate applicability of the TV tomography algorithm using in vivo ultrasound breast data from 61 patients, and compare the results with those obtained using the Tikhonov regularization method. We demonstrate that, compared to the Tikhonov regularization scheme, the TV regularization method significantly improves image quality, resulting in sound-speed tomography images with sharp (preserved) edges of abnormalities and few artifacts.
Manufacture of Regularly Shaped Sol-Gel Pellets
Leventis, Nicholas; Johnston, James C.; Kinder, James D.
2006-01-01
An extrusion batch process for manufacturing regularly shaped sol-gel pellets has been devised as an improved alternative to a spray process that yields irregularly shaped pellets. The aspect ratio of regularly shaped pellets can be controlled more easily, while regularly shaped pellets pack more efficiently. In the extrusion process, a wet gel is pushed out of a mold and chopped repetitively into short, cylindrical pieces as it emerges from the mold. The pieces are collected and can be either (1) dried at ambient pressure to xerogel, (2) solvent exchanged and dried under ambient pressure to ambigels, or (3) supercritically dried to aerogel. Advantageously, the extruded pellets can be dropped directly in a cross-linking bath, where they develop a conformal polymer coating around the skeletal framework of the wet gel via reaction with the cross linker. These pellets can be dried to mechanically robust X-Aerogel.
Gamma regularization based reconstruction for low dose CT
International Nuclear Information System (INIS)
Zhang, Junfeng; Chen, Yang; Hu, Yining; Luo, Limin; Shu, Huazhong; Li, Bicao; Liu, Jin; Coatrieux, Jean-Louis
2015-01-01
Reducing the radiation in computerized tomography is today a major concern in radiology. Low dose computerized tomography (LDCT) offers a sound way to deal with this problem. However, more severe noise in the reconstructed CT images is observed under low dose scan protocols (e.g. lowered tube current or voltage values). In this paper we propose a Gamma regularization based algorithm for LDCT image reconstruction. This solution is flexible and provides a good balance between the regularizations based on l 0 -norm and l 1 -norm. We evaluate the proposed approach using the projection data from simulated phantoms and scanned Catphan phantoms. Qualitative and quantitative results show that the Gamma regularization based reconstruction can perform better in both edge-preserving and noise suppression when compared with other norms. (paper)
Further investigation on "A multiplicative regularization for force reconstruction"
Aucejo, M.; De Smet, O.
2018-05-01
We have recently proposed a multiplicative regularization to reconstruct mechanical forces acting on a structure from vibration measurements. This method does not require any selection procedure for choosing the regularization parameter, since the amount of regularization is automatically adjusted throughout an iterative resolution process. The proposed iterative algorithm has been developed with performance and efficiency in mind, but it is actually a simplified version of a full iterative procedure not described in the original paper. The present paper aims at introducing the full resolution algorithm and comparing it with its simplified version in terms of computational efficiency and solution accuracy. In particular, it is shown that both algorithms lead to very similar identified solutions.
Structural characterization of the packings of granular regular polygons.
Wang, Chuncheng; Dong, Kejun; Yu, Aibing
2015-12-01
By using a recently developed method for discrete modeling of nonspherical particles, we simulate the random packings of granular regular polygons with three to 11 edges under gravity. The effects of shape and friction on the packing structures are investigated by various structural parameters, including packing fraction, the radial distribution function, coordination number, Voronoi tessellation, and bond-orientational order. We find that packing fraction is generally higher for geometrically nonfrustrated regular polygons, and can be increased by the increase of edge number and decrease of friction. The changes of packing fraction are linked with those of the microstructures, such as the variations of the translational and orientational orders and local configurations. In particular, the free areas of Voronoi tessellations (which are related to local packing fractions) can be described by log-normal distributions for all polygons. The quantitative analyses establish a clearer picture for the packings of regular polygons.
Manifestly scale-invariant regularization and quantum effective operators
Ghilencea, D.M.
2016-01-01
Scale invariant theories are often used to address the hierarchy problem, however the regularization of their quantum corrections introduces a dimensionful coupling (dimensional regularization) or scale (Pauli-Villars, etc) which break this symmetry explicitly. We show how to avoid this problem and study the implications of a manifestly scale invariant regularization in (classical) scale invariant theories. We use a dilaton-dependent subtraction function $\\mu(\\sigma)$ which after spontaneous breaking of scale symmetry generates the usual DR subtraction scale $\\mu(\\langle\\sigma\\rangle)$. One consequence is that "evanescent" interactions generated by scale invariance of the action in $d=4-2\\epsilon$ (but vanishing in $d=4$), give rise to new, finite quantum corrections. We find a (finite) correction $\\Delta U(\\phi,\\sigma)$ to the one-loop scalar potential for $\\phi$ and $\\sigma$, beyond the Coleman-Weinberg term. $\\Delta U$ is due to an evanescent correction ($\\propto\\epsilon$) to the field-dependent masses (of...
Low-rank matrix approximation with manifold regularization.
Zhang, Zhenyue; Zhao, Keke
2013-07-01
This paper proposes a new model of low-rank matrix factorization that incorporates manifold regularization to the matrix factorization. Superior to the graph-regularized nonnegative matrix factorization, this new regularization model has globally optimal and closed-form solutions. A direct algorithm (for data with small number of points) and an alternate iterative algorithm with inexact inner iteration (for large scale data) are proposed to solve the new model. A convergence analysis establishes the global convergence of the iterative algorithm. The efficiency and precision of the algorithm are demonstrated numerically through applications to six real-world datasets on clustering and classification. Performance comparison with existing algorithms shows the effectiveness of the proposed method for low-rank factorization in general.
Selecting protein families for environmental features based on manifold regularization.
Jiang, Xingpeng; Xu, Weiwei; Park, E K; Li, Guangrong
2014-06-01
Recently, statistics and machine learning have been developed to identify functional or taxonomic features of environmental features or physiological status. Important proteins (or other functional and taxonomic entities) to environmental features can be potentially used as biosensors. A major challenge is how the distribution of protein and gene functions embodies the adaption of microbial communities across environments and host habitats. In this paper, we propose a novel regularization method for linear regression to adapt the challenge. The approach is inspired by local linear embedding (LLE) and we call it a manifold-constrained regularization for linear regression (McRe). The novel regularization procedure also has potential to be used in solving other linear systems. We demonstrate the efficiency and the performance of the approach in both simulation and real data.
Processing SPARQL queries with regular expressions in RDF databases
2011-01-01
Background As the Resource Description Framework (RDF) data model is widely used for modeling and sharing a lot of online bioinformatics resources such as Uniprot (dev.isb-sib.ch/projects/uniprot-rdf) or Bio2RDF (bio2rdf.org), SPARQL - a W3C recommendation query for RDF databases - has become an important query language for querying the bioinformatics knowledge bases. Moreover, due to the diversity of users’ requests for extracting information from the RDF data as well as the lack of users’ knowledge about the exact value of each fact in the RDF databases, it is desirable to use the SPARQL query with regular expression patterns for querying the RDF data. To the best of our knowledge, there is currently no work that efficiently supports regular expression processing in SPARQL over RDF databases. Most of the existing techniques for processing regular expressions are designed for querying a text corpus, or only for supporting the matching over the paths in an RDF graph. Results In this paper, we propose a novel framework for supporting regular expression processing in SPARQL query. Our contributions can be summarized as follows. 1) We propose an efficient framework for processing SPARQL queries with regular expression patterns in RDF databases. 2) We propose a cost model in order to adapt the proposed framework in the existing query optimizers. 3) We build a prototype for the proposed framework in C++ and conduct extensive experiments demonstrating the efficiency and effectiveness of our technique. Conclusions Experiments with a full-blown RDF engine show that our framework outperforms the existing ones by up to two orders of magnitude in processing SPARQL queries with regular expression patterns. PMID:21489225
Processing SPARQL queries with regular expressions in RDF databases
Directory of Open Access Journals (Sweden)
Cho Hune
2011-03-01
Full Text Available Abstract Background As the Resource Description Framework (RDF data model is widely used for modeling and sharing a lot of online bioinformatics resources such as Uniprot (dev.isb-sib.ch/projects/uniprot-rdf or Bio2RDF (bio2rdf.org, SPARQL - a W3C recommendation query for RDF databases - has become an important query language for querying the bioinformatics knowledge bases. Moreover, due to the diversity of users’ requests for extracting information from the RDF data as well as the lack of users’ knowledge about the exact value of each fact in the RDF databases, it is desirable to use the SPARQL query with regular expression patterns for querying the RDF data. To the best of our knowledge, there is currently no work that efficiently supports regular expression processing in SPARQL over RDF databases. Most of the existing techniques for processing regular expressions are designed for querying a text corpus, or only for supporting the matching over the paths in an RDF graph. Results In this paper, we propose a novel framework for supporting regular expression processing in SPARQL query. Our contributions can be summarized as follows. 1 We propose an efficient framework for processing SPARQL queries with regular expression patterns in RDF databases. 2 We propose a cost model in order to adapt the proposed framework in the existing query optimizers. 3 We build a prototype for the proposed framework in C++ and conduct extensive experiments demonstrating the efficiency and effectiveness of our technique. Conclusions Experiments with a full-blown RDF engine show that our framework outperforms the existing ones by up to two orders of magnitude in processing SPARQL queries with regular expression patterns.
Processing SPARQL queries with regular expressions in RDF databases.
Lee, Jinsoo; Pham, Minh-Duc; Lee, Jihwan; Han, Wook-Shin; Cho, Hune; Yu, Hwanjo; Lee, Jeong-Hoon
2011-03-29
As the Resource Description Framework (RDF) data model is widely used for modeling and sharing a lot of online bioinformatics resources such as Uniprot (dev.isb-sib.ch/projects/uniprot-rdf) or Bio2RDF (bio2rdf.org), SPARQL - a W3C recommendation query for RDF databases - has become an important query language for querying the bioinformatics knowledge bases. Moreover, due to the diversity of users' requests for extracting information from the RDF data as well as the lack of users' knowledge about the exact value of each fact in the RDF databases, it is desirable to use the SPARQL query with regular expression patterns for querying the RDF data. To the best of our knowledge, there is currently no work that efficiently supports regular expression processing in SPARQL over RDF databases. Most of the existing techniques for processing regular expressions are designed for querying a text corpus, or only for supporting the matching over the paths in an RDF graph. In this paper, we propose a novel framework for supporting regular expression processing in SPARQL query. Our contributions can be summarized as follows. 1) We propose an efficient framework for processing SPARQL queries with regular expression patterns in RDF databases. 2) We propose a cost model in order to adapt the proposed framework in the existing query optimizers. 3) We build a prototype for the proposed framework in C++ and conduct extensive experiments demonstrating the efficiency and effectiveness of our technique. Experiments with a full-blown RDF engine show that our framework outperforms the existing ones by up to two orders of magnitude in processing SPARQL queries with regular expression patterns.
REGULARIZED D-BAR METHOD FOR THE INVERSE CONDUCTIVITY PROBLEM
DEFF Research Database (Denmark)
Knudsen, Kim; Lassas, Matti; Mueller, Jennifer
2009-01-01
A strategy for regularizing the inversion procedure for the two-dimensional D-bar reconstruction algorithm based on the global uniqueness proof of Nachman [Ann. Math. 143 (1996)] for the ill-posed inverse conductivity problem is presented. The strategy utilizes truncation of the boundary integral...... the convergence of the reconstructed conductivity to the true conductivity as the noise level tends to zero. The results provide a link between two traditions of inverse problems research: theory of regularization and inversion methods based on complex geometrical optics. Also, the procedure is a novel...
Arithmetic properties of $\\ell$-regular overpartition pairs
NAIKA, MEGADAHALLI SIDDA MAHADEVA; SHIVASHANKAR, CHANDRAPPA
2017-01-01
In this paper, we investigate the arithmetic properties of $\\ell$-regular overpartition pairs. Let $\\overline{B}_{\\ell}(n)$ denote the number of $\\ell$-regular overpartition pairs of $n$. We will prove the number of Ramanujan-like congruences and infinite families of congruences modulo 3, 8, 16, 36, 48, 96 for $\\overline{B}_3(n)$ and modulo 3, 16, 64, 96 for $\\overline{B}_4(n)$. For example, we find that for all nonnegative integers $\\alpha$ and $n$, $\\overline{B}_{3}(3^{\\alpha}(3n+2))\\equiv ...
Sparse reconstruction by means of the standard Tikhonov regularization
International Nuclear Information System (INIS)
Lu Shuai; Pereverzev, Sergei V
2008-01-01
It is a common belief that Tikhonov scheme with || · ||L 2 -penalty fails in sparse reconstruction. We are going to show, however, that this standard regularization can help if the stability measured in L 1 -norm will be properly taken into account in the choice of the regularization parameter. The crucial point is that now a stability bound may depend on the bases with respect to which the solution of the problem is assumed to be sparse. We discuss how such a stability can be estimated numerically and present the results of computational experiments giving the evidence of the reliability of our approach.
Regularization Techniques for Linear Least-Squares Problems
Suliman, Mohamed
2016-04-01
Linear estimation is a fundamental branch of signal processing that deals with estimating the values of parameters from a corrupted measured data. Throughout the years, several optimization criteria have been used to achieve this task. The most astonishing attempt among theses is the linear least-squares. Although this criterion enjoyed a wide popularity in many areas due to its attractive properties, it appeared to suffer from some shortcomings. Alternative optimization criteria, as a result, have been proposed. These new criteria allowed, in one way or another, the incorporation of further prior information to the desired problem. Among theses alternative criteria is the regularized least-squares (RLS). In this thesis, we propose two new algorithms to find the regularization parameter for linear least-squares problems. In the constrained perturbation regularization algorithm (COPRA) for random matrices and COPRA for linear discrete ill-posed problems, an artificial perturbation matrix with a bounded norm is forced into the model matrix. This perturbation is introduced to enhance the singular value structure of the matrix. As a result, the new modified model is expected to provide a better stabilize substantial solution when used to estimate the original signal through minimizing the worst-case residual error function. Unlike many other regularization algorithms that go in search of minimizing the estimated data error, the two new proposed algorithms are developed mainly to select the artifcial perturbation bound and the regularization parameter in a way that approximately minimizes the mean-squared error (MSE) between the original signal and its estimate under various conditions. The first proposed COPRA method is developed mainly to estimate the regularization parameter when the measurement matrix is complex Gaussian, with centered unit variance (standard), and independent and identically distributed (i.i.d.) entries. Furthermore, the second proposed COPRA
Adiabatic regularization of power spectra in nonminimally coupled chaotic inflation
Energy Technology Data Exchange (ETDEWEB)
Alinea, Allan L., E-mail: alinea@het.phys.sci.osaka-u.ac.jp [Department of Physics, Osaka University, Toyonaka, Osaka 560-0043 (Japan)
2016-10-01
We investigate the effect of adiabatic regularization on both the tensor- and scalar-perturbation power spectra in nonminimally coupled chaotic inflation. Similar to that of the minimally coupled general single-field inflation, we find that the subtraction term is suppressed by an exponentially decaying factor involving the number of e -folds. By following the subtraction term long enough beyond horizon crossing, the regularized power spectrum tends to the ''bare'' power spectrum. This study justifies the use of the unregularized (''bare'') power spectrum in standard calculations.
Lifshitz anomalies, Ward identities and split dimensional regularization
Energy Technology Data Exchange (ETDEWEB)
Arav, Igal; Oz, Yaron; Raviv-Moshe, Avia [Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University,55 Haim Levanon street, Tel-Aviv, 69978 (Israel)
2017-03-16
We analyze the structure of the stress-energy tensor correlation functions in Lifshitz field theories and construct the corresponding anomalous Ward identities. We develop a framework for calculating the anomaly coefficients that employs a split dimensional regularization and the pole residues. We demonstrate the procedure by calculating the free scalar Lifshitz scale anomalies in 2+1 spacetime dimensions. We find that the analysis of the regularization dependent trivial terms requires a curved spacetime description without a foliation structure. We discuss potential ambiguities in Lifshitz scale anomaly definitions.
Stability of negative ionization fronts: Regularization by electric screening?
International Nuclear Information System (INIS)
Arrayas, Manuel; Ebert, Ute
2004-01-01
We recently have proposed that a reduced interfacial model for streamer propagation is able to explain spontaneous branching. Such models require regularization. In the present paper we investigate how transversal Fourier modes of a planar ionization front are regularized by the electric screening length. For a fixed value of the electric field ahead of the front we calculate the dispersion relation numerically. These results guide the derivation of analytical asymptotes for arbitrary fields: for small wave-vector k, the growth rate s(k) grows linearly with k, for large k, it saturates at some positive plateau value. We give a physical interpretation of these results
Spanning k-ended trees of 3-regular connected graphs
Directory of Open Access Journals (Sweden)
Hamed Ghasemian Zoeram
2017-10-01
Full Text Available A vertex of degree one is called an end-vertex and the set of end-vertices of G is denoted by End(G. For a positive integer k, a tree T be called k-ended tree if $|End(T| \\leq k$. In this paper, we obtain sufficient conditions for spanning k-trees of 3-regular connected graphs. We give a construction sequence of graphs satisfying the condition. At the end, we present a conjecture about spanning k-ended trees of 3-regular connected graphs.
Mathematical Modeling the Geometric Regularity in Proteus Mirabilis Colonies
Zhang, Bin; Jiang, Yi; Minsu Kim Collaboration
Proteus Mirabilis colony exhibits striking spatiotemporal regularity, with concentric ring patterns with alternative high and low bacteria density in space, and periodicity for repetition process of growth and swarm in time. We present a simple mathematical model to explain the spatiotemporal regularity of P. Mirabilis colonies. We study a one-dimensional system. Using a reaction-diffusion model with thresholds in cell density and nutrient concentration, we recreated periodic growth and spread patterns, suggesting that the nutrient constraint and cell density regulation might be sufficient to explain the spatiotemporal periodicity in P. Mirabilis colonies. We further verify this result using a cell based model.
Parameter optimization in the regularized kernel minimum noise fraction transformation
DEFF Research Database (Denmark)
Nielsen, Allan Aasbjerg; Vestergaard, Jacob Schack
2012-01-01
Based on the original, linear minimum noise fraction (MNF) transformation and kernel principal component analysis, a kernel version of the MNF transformation was recently introduced. Inspired by we here give a simple method for finding optimal parameters in a regularized version of kernel MNF...... analysis. We consider the model signal-to-noise ratio (SNR) as a function of the kernel parameters and the regularization parameter. In 2-4 steps of increasingly refined grid searches we find the parameters that maximize the model SNR. An example based on data from the DLR 3K camera system is given....
Lifshitz anomalies, Ward identities and split dimensional regularization
International Nuclear Information System (INIS)
Arav, Igal; Oz, Yaron; Raviv-Moshe, Avia
2017-01-01
We analyze the structure of the stress-energy tensor correlation functions in Lifshitz field theories and construct the corresponding anomalous Ward identities. We develop a framework for calculating the anomaly coefficients that employs a split dimensional regularization and the pole residues. We demonstrate the procedure by calculating the free scalar Lifshitz scale anomalies in 2+1 spacetime dimensions. We find that the analysis of the regularization dependent trivial terms requires a curved spacetime description without a foliation structure. We discuss potential ambiguities in Lifshitz scale anomaly definitions.
Quirino, Angela; Pulcrano, Giovanna; Rametti, Linda; Puccio, Rossana; Marascio, Nadia; Catania, Maria Rosaria; Matera, Giovanni; Liberto, Maria Carla; Focà, Alfredo
2014-03-22
Ochrobactrum anthropi (O. anthropi), is a non-fermenting gram-negative bacillus usually found in the environment. Nevertheless, during the past decade it has been identified as pathogenic to immunocompromised patients. In this study, we assessed the usefulness of the automated repetitive extragenic palindromic-polymerase chain reaction (rep-PCR-based DiversiLab™ system, bioMèrieux, France) and of matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF MS) for typing of twentythree O. anthropi clinical isolates that we found over a four-months period (from April 2011 to August 2011) in bacteriemic patients admitted in the same operative unit of our hospital. Pulsed-field gel electrophoresis (PFGE), commonly accepted as the gold standard technique for typing, was also used. Analysis was carried out using the Pearson correlation coefficient to determine the distance matrice and the unweighted pair group method with arithmetic mean (UPGMA) to generate dendogram. Rep-PCR analysis identified four different patterns: three that clustered together with 97% or more pattern similarity, and one whose members showed < 95% pattern similarity. Interestingly, strains isolated later (from 11/06/2011 to 24/08/2011) displayed a pattern with 99% similarity. MALDI-TOF MS evaluation clustered the twentythree strains of O. anthropi into a single group containing four distinct subgroups, each comprising the majority of strains clustering below 5 distance levels, indicating a high similarity between the isolates. Our results indicate that these isolates are clonally-related and the methods used afforded a valuable contribution to the epidemiology, prevention and control of the infections caused by this pathogen.
Jaballah, Soumeya Ali; Aktar, Suriya J; Ali, Jahabar; Phillip, Pretty Susan; Al Dhaheri, Noura Salem; Jabeen, Aayesha; Rizvi, Tahir A
2010-09-03
During retroviral RNA packaging, two copies of genomic RNA are preferentially packaged into the budding virus particles whereas the spliced viral RNAs and the cellular RNAs are excluded during this process. Specificity towards retroviral RNA packaging is dependent upon sequences at the 5' end of the viral genome, which at times extend into Gag sequences. It has earlier been suggested that the Mason-Pfizer monkey virus (MPMV) contains packaging sequences within the 5' untranslated region (UTR) and Gag. These studies have also suggested that the packaging determinants of MPMV that lie in the UTR are bipartite and are divided into two regions both upstream and downstream of the major splice donor. However, the precise boundaries of these discontinuous regions within the UTR and the role of the intervening sequences between these dipartite sequences towards MPMV packaging have not been investigated. Employing a combination of genetic and structural prediction analyses, we have shown that region "A", immediately downstream of the primer binding site, is composed of 50 nt, whereas region "B" is composed of the last 23 nt of UTR, and the intervening 55 nt between these two discontinuous regions do not contribute towards MPMV RNA packaging. In addition, we have identified a 14-nt G-C-rich palindromic sequence (with 100% autocomplementarity) within region A that has been predicted to fold into a structural motif and is essential for optimal MPMV RNA packaging. Furthermore, we have also identified a stretch of single-stranded purines (ssPurines) within the UTR and 8 nt of these ssPurines are duplicated in region B. The native ssPurines or its repeat in region B when predicted to refold as ssPurines has been shown to be essential for RNA packaging, possibly functioning as a potential nucleocapsid binding site. Findings from this study should enhance our understanding of the steps involved in MPMV replication including RNA encapsidation process. Copyright (c) 2010 Elsevier Ltd