| 1. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
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| 3. |
- Abernethy, R. J., et al.
(författare)
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Poly(methimazolyl)borato nitrosyl complexes of molybdenum and tungsten
- 2008
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Ingår i: Organometallics. - : American Chemical Society (ACS). - 0276-7333 .- 1520-6041. ; 27:17, s. 4455-4463
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Tidskriftsartikel (refereegranskat)abstract
- The syntheses of a range of poly(methimazolyl)borate -ligated nitrosyl complexes of tungsten and molybdenum are reported, the characterization of which includes the crystal structure determinations of the compounds [W(NO)(CO)(2){k(3)-S,S',S''-HB(mt)(3)}], [W(NO)(CO)(2)(PPh3){k(2)-S,S'-H2B(mt)(2)}], and [Mo(NO-)(CO)(2) {k(3)-H,S,S'-H2B(mt)(2)}] (mt = methimazoyl). The reaction of [W(NO)(CO)(3)(PPh3)(2)]PF6 with Na[HB(mt)(3)] and Na[H2B(mt)(2)}] provides respectively [W(NO)(CO)(2)[HB(mt)(3)] and [W(NO)(CO)(2)(PPh3){k(2_) S,S'-H2B(mt)(2)}]. The complexes [M(NO)(CO)(2){HB(mt)(3)}] and [M(NO)(CO)(2){k(3)-H,S,S'-H2B(mt)(2)}] (M = W, Mo) arise from the reactions of Na[M(CO)(3){H2B(mt)(2)}] with N-methyl-N-nitrosotoluenesulfonamide. The molybdenum complex [Mo(NO)(CO)(2){HB(mt)(3)}] is also obtained unexpectedly from the reaction of [MO(eta(3)-C3H5)(CO)(2){HB(mt)(3)}] with [NO]BF4.
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| 4. |
- Adcox, K, et al.
(författare)
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Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX Collaboration
- 2005
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Ingår i: Nuclear Physics, Section A. - : Elsevier BV. - 0375-9474. ; 757:1-2, s. 184-283
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Forskningsöversikt (refereegranskat)abstract
- Extensive experimental data from high-energy nucleus-nucleus collisions were recorded using the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The comprehensive set of measurements from the first three years of RHIC operation includes charged particle multiplicities, transverse energy, yield ratios and spectra of identified hadrons in a wide range of transverse momenta (PT), elliptic flow, two-particle correlations, nonstatistical fluctuations, and suppression of particle production at high PT. The results are examined with an emphasis on implications for the formation of a new state of dense matter. We find that the state of matter created at RHIC cannot be described in terms of ordinary color neutral hadrons.
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| 5. |
- Adewumi, Oluseun, et al.
(författare)
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Characterization of human embryonic stem cell lines by the International Stem Cell Initiative
- 2007
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Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 25:7, s. 803-816
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Tidskriftsartikel (refereegranskat)abstract
- The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue- nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.
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| 6. |
- Alm, Håkan, et al.
(författare)
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Work domain analysis of driving information
- 2009
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Konferensbidrag (refereegranskat)abstract
- In order to drive in a safe and environmentally friendly manner a driver needs support on the skillbased, rule based and knowledge based level (Rasmussen, 1986). It can be argued that today's driverinformation mainly supports skill and rule based levels while the complex task of driving also needssupport on the knowledge based level, e.g. problem solving . The aim of this study was to identifyways to support problem solving and decision making in a driving information context and to studygaps, overlaps, strong and weak relations between the driver information functions and the purpose ofthe functions.Work Domain Analysis (WDA) (Vicente, 1999) was used to decompose the purpose of the driverinformation down to the component level. WDA is the first step of five in Cognitive Work Analysis(CWA). CWA belongs to the category of Ecological Interface Design that aims to aid the design ofhuman centred interfaces and systems that support problem solving and decision making in complexsocio-technical systems.The study was performed by researchers from Luleå University of Technology and Volvo Cars as wellas members of a Driving information project. The study was limited to driver information systems inprivate cars which means that the main purpose of the systems was to support drivers' goals e.g.navigate or maintain speed but also being environment friendly, etc. It should also be mentioned thatdriver information not only was limited to information within the car. Before and after driving was alsoincluded. The WDA identified five functional purposes of driving information: To support safe,efficient, environment friendly, legal and enjoyable transportation.The "Functional purpose" was decomposed into "abstract functions" e.g. support choice oftransportation, reduce energy exposure, improve friction, and maintain lateral and longitudinal distance.Further decomposition down to "physical form" showed several weak and some unexpected relationsbetween the purpose and the system. For instance, one conclusion was that the relation betweenspeedometer and safety was weak. The weak relations and the gaps then served as input for designimplications.In the design implications part it was concluded that planning could be improved in comparison withtoday's systems by e.g. internet services and pre- and post-trip information. New features in thenavigation system, such as route optimization based on safety or carbon footprint, could improve bothsafety and environmental friendliness. Feedback or Edutainment (Education by Entertainment) couldalso serve as a way to improve safety and green driving. A rather controversial and perhaps unrealisticsuggestion is that a private car could provide statistics or data about safety, environmental friendlinessor efficiency (Cost) for different types of transportation in order to make the choice of transportationoptimized.Another, more general conclusion is that the decomposition also showed the importance for a designerto ask the question "why?" when designing a product.
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| 7. |
- Benninger, Richard K. P., et al.
(författare)
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Live Cell Linear Dichroism Imaging Reveals Extensive Membrane Ruffling within the Docking Structure of Natural Killer Cell Immune Synapses
- 2009
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 96:2, s. L13-L15
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Tidskriftsartikel (refereegranskat)abstract
- We have applied fluorescence imaging of two-photon linear dichroism to measure the subresolution organization of the cell membrane during formation of the activating (cytolytic) natural killer (NK) cell immune synapse (IS). This approach revealed that the NK cell plasma membrane is convoluted into ruffles at the periphery, but not in the center of a mature cytolytic NK cell IS. Time-lapse imaging showed that the membrane ruffles formed at the initial point of contact between NK cells and target cells and then spread radialy across the intercellular contact as the size of the IS increased, becoming absent from the center of the mature synapse. Understanding the role of such extensive membrane ruff ling in the assembly of cytolytic synapses is an intriguing new goal.
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| 8. |
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| 9. |
- Champion, Mia D, et al.
(författare)
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Comparative genomic characterization of Francisella tularensis strains belonging to low and high virulence subspecies
- 2009
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Ingår i: PLoS pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 5:5, s. e1000459-
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Tidskriftsartikel (refereegranskat)abstract
- Tularemia is a geographically widespread, severely debilitating, and occasionally lethal disease in humans. It is caused by infection by a gram-negative bacterium, Francisella tularensis. In order to better understand its potency as an etiological agent as well as its potential as a biological weapon, we have completed draft assemblies and report the first complete genomic characterization of five strains belonging to the following different Francisella subspecies (subsp.): the F. tularensis subsp. tularensis FSC033, F. tularensis subsp. holarctica FSC257 and FSC022, and F. tularensis subsp. novicida GA99-3548 and GA99-3549 strains. Here, we report the sequencing of these strains and comparative genomic analysis with recently available public Francisella sequences, including the rare F. tularensis subsp. mediasiatica FSC147 strain isolate from the Central Asian Region. We report evidence for the occurrence of large-scale rearrangement events in strains of the holarctica subspecies, supporting previous proposals that further phylogenetic subdivisions of the Type B clade are likely. We also find a significant enrichment of disrupted or absent ORFs proximal to predicted breakpoints in the FSC022 strain, including a genetic component of the Type I restriction-modification defense system. Many of the pseudogenes identified are also disrupted in the closely related rarely human pathogenic F. tularensis subsp. mediasiatica FSC147 strain, including modulator of drug activity B (mdaB) (FTT0961), which encodes a known NADPH quinone reductase involved in oxidative stress resistance. We have also identified genes exhibiting sequence similarity to effectors of the Type III (T3SS) and components of the Type IV secretion systems (T4SS). One of the genes, msrA2 (FTT1797c), is disrupted in F. tularensis subsp. mediasiatica and has recently been shown to mediate bacterial pathogen survival in host organisms. Our findings suggest that in addition to the duplication of the Francisella Pathogenicity Island, and acquisition of individual loci, adaptation by gene loss in the more recently emerged tularensis, holarctica, and mediasiatica subspecies occurred and was distinct from evolutionary events that differentiated these subspecies, and the novicida subspecies, from a common ancestor. Our findings are applicable to future studies focused on variations in Francisella subspecies pathogenesis, and of broader interest to studies of genomic pathoadaptation in bacteria.
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| 10. |
- Chapin III, F.S., et al.
(författare)
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Polar Systems
- 2006
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Ingår i: Millenium Ecosystem Assessment 2005 - Current State and Trends. - 1559632283 - 9781559632287 ; 1
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 11. |
- de Bakker, Paul I. W., et al.
(författare)
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Transferability of tag SNPs in genetic association studies in multiple populations
- 2006
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 38:11, s. 1298-1303
-
Tidskriftsartikel (refereegranskat)abstract
- A general question for linkage disequilibrium-based association studies is how power to detect an association is compromised when tag SNPs are chosen from data in one population sample and then deployed in another sample. Specifically, it is important to know how well tags picked from the HapMap DNA samples capture the variation in other samples. To address this, we collected dense data uniformly across the four HapMap population samples and eleven other population samples. We picked tag SNPs using genotype data we collected in the HapMap samples and then evaluated the effective coverage of these tags in comparison to the entire set of common variants observed in the other samples. We simulated case-control association studies in the non-HapMap samples under a disease model of modest risk, and we observed little loss in power. These results demonstrate that the HapMap DNA samples can be used to select tags for genome-wide association studies in many samples around the world.
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| 12. |
- Laslett, Mark, et al.
(författare)
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Diagnosis of Sacroiliac Joint Pain : Validity of individual provocation tests and composites of tests
- 2005
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Ingår i: Manual Therapy. - : Elsevier BV. - 1356-689X .- 1532-2769. ; 10:3, s. 207-218
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Tidskriftsartikel (refereegranskat)abstract
- Previous research indicates that physical examination cannot diagnose sacroiliac joint (SIJ) pathology. Earlier studies have not reported sensitivities and specificities of composites of provocation tests known to have acceptable inter-examiner reliability. This study examined the diagnostic power of pain provocation SIJ tests singly and in various combinations, in relation to an accepted criterion standard. In a blinded criterion-related validity design, 48 patients were examined by physiotherapists using pain provocation SIJ tests and received an injection of local anaesthetic into the SIJ. The tests were evaluated singly and in various combinations (composites) for diagnostic power. All patients with a positive response to diagnostic injection reported pain with at least one SIJ test. Sensitivity and specificity for three or more of six positive SIJ tests were 94% and 78%, respectively. Receiver operator characteristic curves and areas under the curve were constructed for various composites. The greatest area under the curve for any two of the best four tests was 0.842. In conclusion, composites of provocation SIJ tests are of value in clinical diagnosis of symptomatic SIJ. Three or more out of six tests or any two of four selected tests have the best predictive power in relation to results of intra-articular anaesthetic block injections. When all six provocation tests do not provoke familiar pain, the SIJ can be ruled out as a source of current LBP. © 2005 Elsevier Ltd. All rights reserved.
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| 13. |
- Lindblad-Toh, Kerstin, et al.
(författare)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Tidskriftsartikel (refereegranskat)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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| 14. |
- Liu, Wing Kam, et al.
(författare)
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Complexity science of multiscale materials via stochastic computations
- 2009
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Ingår i: International Journal for Numerical Methods in Engineering. - : Wiley. - 0029-5981 .- 1097-0207. ; 80:6-7, s. 932-978
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Tidskriftsartikel (refereegranskat)abstract
- New technological advances today allow for a range of advanced composite materials, including multilayer materials and nanofiber-matrix composites. In this context, the key to developing advanced materials IS file understanding of the interplay between the various physical scales present. from the atomic level Interactions to the microstructaral composition and the marcoscale behavior Using the developing 'multiresolution data sets mechanics' the 'predictive science-based governing laws of the materials microstructure evolutions' are derived and Melted into a 'stochastic multiresolution design framework' Under such a framework. the governing laws Of the materials microstructure evolution will be essential to assess, across multiple scales. The impact of multiscale material design. geometry design of a structure and the manufacturing process conditions, by following the cause-effect relationship from structure property and then to performance The future Integrated multiscale analysis system will be Constructed based on a probabilistic complexity science-based mathematical framework. its verification, validation and uncertainty quantification tire done through carefully designed experiments, and file life-cycled materials design for products design and manufacturing is performed through the use of petascale computing. The various techniques of microstructure reconstruction result in the genetation of model microstructures that, at some level, has the same statistical properties as the real heterogenous media. Having reconstructed the heterogeneous medium. one can then evaluate Its effective properties via direct numerical simulation and compare these values with experimentally measured properties of the actual medium. The proposed analysis will be dynamic in nature to capture the multi-stage historical evolvement of material/structure performance over the life span of a product. In addition to providing more accurate assessment of structure performance with stochastic multiscale analysis. our development will provide the capability of predicting failures and system reliability to enable more reliable design and decisions in product development.
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| 15. |
- Minehira, Kaori, et al.
(författare)
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Blocking VLDL secretion causes hepatic steatosis but does not affect peripheral lipid stores or insulin sensitivity in mice
- 2008
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Ingår i: Journal of Lipid Research. - : American Society for Biochemistry and Molecular Biology. - 0022-2275 .- 1539-7262. ; 49:9, s. 2038-2044
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Tidskriftsartikel (refereegranskat)abstract
- The liver secretes triglyceride-rich VLDLs, and the triglycerides in these particles are taken up by peripheral tissues, mainly heart, skeletal muscle, and adipose tissue. Blocking hepatic VLDL secretion interferes with the delivery of liver-derived triglycerides to peripheral tissues and results in an accumulation of triglycerides in the liver. However, it is unclear how interfering with hepatic triglyceride secretion affects adiposity, muscle triglyceride stores, and insulin sensitivity. To explore these issues, we examined mice that cannot secrete VLDL [due to the absence of microsomal triglyceride transfer protein (Mttp) in the liver]. These mice exhibit markedly reduced levels of apolipoprotein B-100 in the plasma, along with reduced levels of triglycerides in the plasma. Despite the low plasma triglyceride levels, triglyceride levels in skeletal muscle were unaffected. Adiposity and adipose tissue triglyceride synthesis rates were also normal, and body weight curves were unaffected. Even though the blockade of VLDL secretion caused hepatic steatosis accompanied by increased ceramides and diacylglycerols in the liver, the mice exhibited normal glucose tolerance and were sensitive to insulin at the whole-body level, as judged by hyperinsulinemic euglycemic clamp studies. Normal hepatic glucose production and insulin signaling were also maintained in the fatty liver induced by Mttp deletion. Thus, blocking VLDL secretion causes hepatic steatosis without insulin resistance, and there is little effect on muscle triglyceride stores or adiposity.
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| 16. |
- Poulton, Alex J., et al.
(författare)
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Phytoplankton carbon fixation, chlorophyll-biomass and diagnostic pigments in the Atlantic Ocean
- 2006
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Ingår i: Deep-sea research. Part II, Topical studies in oceanography. - : Elsevier BV. - 0967-0645 .- 1879-0100. ; 53:14-16, s. 1593-1610
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Tidskriftsartikel (refereegranskat)abstract
- We have made daily measurements of phytoplankton pigments, size-fractionated (< 2 and > 2-mu m) carbon fixation and chlorophyll-a concentration during four Atlantic Meridional Transect (AMT) cruises in 2003-04. Surface rates of carbon fixation ranged from < 0.2-mmol C m(-3) d(-1) in the subtropical gyres to 0.2-0.5-mmol C m(-3) d(-1) in the tropical equatorial Atlantic. Significant intercruise variability was restricted to the subtropical gyres, with higher chlorophyll-a concentrations and carbon fixation in the subsurface chlorophyll maximum during spring in either hemisphere. In surface waters, although picoplankton (<-mu m) represented the dominant fraction in terms of both carbon fixation (50-70%) and chlorophyll-alpha (80-90%), nanoplankton (> 2-mu m) contributions to total carbon fixation (30-50%) were higher than to total chlorophyll-alpha (10-20%). However, in the subsurface chlorophyll maximum picoplankton dominated both carbon fixation (70-90%) and chlorophyll-alpha (70-90%). Thus, in surface waters chlorophyll-normalised carbon fixation was 2-3 times higher for nanoplankton and differences in picoplankton and nanoplankton carbon to chlorophyll-alpha ratios may lead to either higher or similar growth rates. These low chlorophyll-normalised carbon fixation rates for picoplankton may also reflect losses of fixed carbon (cell leakage or respiration), decreases in photosynthetic efficiency, grazing losses during the incubations, or some combination of all these. Comparison of nitrate concentrations in the subsurface chlorophyll maximum with estimates of those required to support the observed rates of carbon fixation (assuming Redfield stoichiometry) indicate that primary production in the chlorophyll maximum may be light rather than nutrient limited.
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| 17. |
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| 18. |
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| 19. |
- Stanton, Neville A., et al.
(författare)
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Predicting pilot error: Testing a new methodology and a multi-methods and analysts approach
- 2009
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Ingår i: Applied Ergonomics. - : Elsevier BV. - 1872-9126 .- 0003-6870. ; 40:3, s. 464-471
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Tidskriftsartikel (refereegranskat)abstract
- The Human Error Template (HET) is a recently developed methodology for predicting design-induced pilot error. This article describes a validation study undertaken to compare the performance of HET against three contemporary Human Error Identification (HEI) approaches when used to predict pilot errors for an approach and landing task and also to compare analyst error predictions to an approach to enhancing error prediction sensitivity: the multiple analysts and methods approach, whereby multiple analyst predictions using a range of HEI techniques are pooled. The findings indicate that, of the four methodologies used in isolation, analysts using the HET methodology offered the most accurate error predictions, and also that the multiple analysts and methods approach was more successful overall in terms of error prediction sensitivity than the three other methods but not the HET approach. The results suggest that when predicting design-induced error, it is appropriate to use a toolkit of different HEI approaches and multiple analysts in order to heighten error prediction sensitivity. (c) 2008 Elsevier Ltd. All rights reserved.
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| 20. |
- Zody, Michael, 1968-, et al.
(författare)
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Analysis of the DNA sequence and duplication history of human chromosome 15
- 2006
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 440:7084, s. 671-675
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Tidskriftsartikel (refereegranskat)abstract
- Here we present a finished sequence of human chromosome 15, together with a high-quality gene catalogue. As chromosome 15 is one of seven human chromosomes with a high rate of segmental duplication, we have carried out a detailed analysis of the duplication structure of the chromosome. Segmental duplication in chromosome 15 are largely clustered in two regions, on proximal and distal 15q; the proximal region is notable because recombination among the segmental duplications can result in deletions causing Prader-Willi and Angelman syndromes. Sequence analysis shows that the proximal and distal regions of 15q share extensive ancient similarity. Using a simple approach, we have been able to reconstruct many of the events by which the current duplication structure arose. We find that most of the intrachromosomal duplications seem to share a common ancestry. Finally, we demonstrate that some remaining gaps in the genome sequence are probably due to structural polymorphisms between haplotypes; this may explain a significant fraction of the gaps remaining in the human genome.
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| 21. |
- Zody, Michael, 1968-, et al.
(författare)
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DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage
- 2006
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 440:7087, s. 1045-1049
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Tidskriftsartikel (refereegranskat)abstract
- Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome. It is also enriched in segmental duplications, ranking third in density among the autosomes. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome.
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