247 research outputs found
Asymptotically Faster Quantum Distributed Algorithms for Approximate Steiner Trees and Directed Minimum Spanning Trees
The CONGEST and CONGEST-CLIQUE models have been carefully studied to
represent situations where the communication bandwidth between processors in a
network is severely limited. Messages of only bits of information
each may be sent between processors in each round. The quantum versions of
these models allow the processors instead to communicate and compute with
quantum bits under the same bandwidth limitations. This leads to the following
natural research question: What problems can be solved more efficiently in
these quantum models than in the classical ones? Building on existing work, we
contribute to this question in two ways. Firstly, we present two algorithms in
the Quantum CONGEST-CLIQUE model of distributed computation that succeed with
high probability; one for producing an approximately optimal Steiner Tree, and
one for producing an exact directed minimum spanning tree, each of which uses
rounds of communication and messages,
where is the number of nodes in the network. The algorithms thus achieve a
lower asymptotic round and message complexity than any known algorithms in the
classical CONGEST-CLIQUE model. At a high level, we achieve these results by
combining classical algorithmic frameworks with quantum subroutines. An
existing framework for using distributed version of Grover's search algorithm
to accelerate triangle finding lies at the core of the asymptotic speedup.
Secondly, we carefully characterize the constants and logarithmic factors
involved in our algorithms as well as related algorithms, otherwise commonly
obscured by notation. The analysis shows that some improvements are
needed to render both our and existing related quantum and classical algorithms
practical, as their asymptotic speedups only help for very large values of .Comment: 23 pages, 0 figure
Mouse Genome-Wide Association Mapping Needs Linkage Analysis to Avoid False-Positive Loci
We carried out genome-wide association (GWA) studies in inbred mouse strains characterized for their lung tumor susceptibility phenotypes (spontaneous or urethane-induced) with panels of 12,959 (13K) or 138,793 (140K) single-nucleotide polymorphisms (SNPs). Above the statistical thresholds, we detected only SNP rs3681853 on Chromosome 5, two SNPs in the pulmonary adenoma susceptibility 1 (Pas1) locus, and SNP rs4174648 on Chromosome 16 for spontaneous tumor incidence, urethane-induced tumor incidence, and urethane-induced tumor multiplicity, respectively, with the 13K SNP panel, but only the Pas1 locus with the 140K SNP panel. Haplotype analysis carried out in the latter panel detected four additional loci. Loci reported in previous GWA studies failed to replicate. Genome-wide genetic linkage analysis in urethane-treated (BALB/c×C3H/He)F2, (BALB/c×SWR/J)F2, and (A/J×C3H/He)F2 mice showed that Pas1, but none of the other loci detected previously or herein by GWA, had a significant effect. The Lasc1 gene, identified by GWA as a functional element (Nat. Genet., 38:888–95, 2006), showed no genetic effects in the two independent intercross mouse populations containing both alleles, nor was it expressed in mouse normal lung or lung tumors. Our results indicate that GWA studies in mouse inbred strains can suffer a high rate of false-positive results and that such an approach should be used in conjunction with classical linkage mapping in genetic crosses
Characterisation of puroindoline genes in wild tetraploid and hexaploid wheats (Triticum araraticum; T. timopheevii and T. zhukovskyi)
Treatment with cisplatin-containing chemotherapy regimens causes hearing loss in 40-60% of cancer patients. It has been suggested that genetic variants in the genes encoding thiopurine S-methyltransferase (TPMT) and catechol O-methyltransferase (COMT) can predict the development of cisplatin-induced ototoxicity and may explain interindividual variability in sensitivity to cisplatin-induced hearing loss. Two recently published studies however, sought to validate these findings and showed inconsistent results. The aim of this study was to evaluate the role of polymorphisms in the TPMT and COMT genes in cisplatin-induced ototoxicity. Therefore we investigated two independent cohorts of 110 Dutch and 38 Spanish patients with osteosarcoma and performed a meta-analysis including all previously published studies resulting in a total population of 664 patients with cancer. With this largest meta-analysis performed to date, we show that the influence of TPMT and COMT on the development of cisplatin-induced hearing loss may be less important than previously suggested
Genomewide high-density SNP linkage analysis of non-BRCA1/2 breast cancer families identifies various candidate regions and has greater power than microsatellite studies
Background: The recent development of new high-throughput technologies for SNP genotyping has opened the possibility of taking a genome-wide linkage approach to the search for new candidate genes involved in heredity diseases. The two major breast cancer susceptibility genes BRCA1 and BRCA2 are involved in 30% of hereditary breast cancer cases, but the discovery of additional breast cancer predisposition genes for the non-BRCA1/2 breast cancer families has so far been unsuccessful. Results: In order to evaluate the power improvement provided by using SNP markers in a real situation, we have performed a whole genome screen of 19 non-BRCA1/2 breast cancer families using 4720 genomewide SNPs with Illumina technology (Illumina's Linkage III Panel), with an average distance of 615 Kb/SNP. We identified six regions on chromosomes 2, 3, 4, 7, 11 and 14 as candidates to contain genes involved in breast cancer susceptibility, and additional fine mapping genotyping using microsatellite markers around linkage peaks confirmed five of them, excluding the region on chromosome 3. These results were consistent in analyses that excluded SNPs in high linkage disequilibrium. The results were compared with those obtained previously using a 10 cM microsatellite scan (STR-GWS) and we found lower or not significant linkage signals with STR-GWS data compared to SNP data in all cases. Conclusion: Our results show the power increase that SNPs can supply in linkage studies
Effect of ABCB1 and ABCC3 Polymorphisms on Osteosarcoma Survival after Chemotherapy: A Pharmacogenetic Study
Standard treatment for osteosarcoma patients consists of a
combination of cisplatin, adriamycin, and methotrexate before surgical resection
of the primary tumour, followed by postoperative chemotherapy including
vincristine and cyclophosphamide. Unfortunately, many patients still relapse or
suffer adverse events. We examined whether common germline polymorphisms in
chemotherapeutic transporter and metabolic pathway genes of the drugs used in
standard osteosarcoma treatment may predict treatment response.
METHODOLOGY/PRINCIPAL FINDINGS: In this study we screened 102 osteosarcoma
patients for 346 Single Nucleotide Polymorphisms (SNPs) and 2 Copy Number
Variants (CNVs) in 24 genes involved in the metabolism or transport of cisplatin,
adriamycin, methotrexate, vincristine, and cyclophosphamide. We studied the
association of the genotypes with tumour response and overall survival. We found
that four SNPs in two ATP-binding cassette genes were significantly associated
with overall survival: rs4148416 in ABCC3 (per-allele HR = 8.14, 95%CI =
2.73-20.2, p-value = 5.1x10(-)(5)), and three SNPs in ABCB1, rs4148737
(per-allele HR = 3.66, 95%CI = 1.85-6.11, p-value = 6.9x10(-)(5)), rs1128503 and
rs10276036 (r(2) = 1, per-allele HR = 0.24, 95%CI = 0.11-0.47 p-value =
7.9x10(-)(5)). Associations with these SNPs remained statistically significant
after correction for multiple testing (all corrected p-values [permutation test]
</= 0.03). CONCLUSIONS: Our findings suggest that these polymorphisms may affect
osteosarcoma treatment efficacy. If these associations are independently
validated, these variants could be used as genetic predictors of clinical outcome
in the treatment of osteosarcoma, helping in the design of individualized
therapy
Estado actual del Banco de Germoplasma Animal en Colombia: organizaciĂłn y manejo
During the last two decades, Colombia has made enormous progress in conserving some of the most relevant zoogenetic resources vital for agricultural production and the food industry. The primary purpose of conserving these local animal genetic resources has been the recovery of these animal breeds (cattle, pigs, and sheep) that presented a high risk of disappearance and therefore establish pure animal collections that allow the researchers to develop conservation programs. Nowadays, these collections are funded by the Colombian government and properly conserved in research centres in AGROSAVIA under in vivo and in vitro conservation systems. The main objective of conserving the local herds has been to maintain the genetic variability of the creole breeds and also generate strategies to strengthen the conservation, characterization and their promotion and use, always considering initiatives that lead to the increase of animal productivity and bearing in mind the threats that creole breeds are facing, such as the intensification of the agricultural production systems, the effects of climate change, and the high maintenance costs incurred by the Animal Germplasm Bank in Colombia. The success of the conservation of animal genetic resources in Colombia will depend to a great extent on the appropriation and acceptance of Colombian farmers for the insertion of these creole breeds in their agricultural production systems. On the other hand, the Animal Germplasm Bank should incorporate in a short period time other species or breeds currently at a high risk of disappearing and important for the agricultural system.En las Ăşltimas dos dĂ©cadas, Colombia ha realizado grandes avances en la conservaciĂłn de algunos de sus recursos zoogenĂ©ticos importantes para la producciĂłn agropecuaria y la alimentaciĂłn. El propĂłsito inicial de conservar estos recursos zoogenĂ©ticos locales, fue el de recuperar razas de animales, principalmente bovinos, porcinos y ovinos que estaban a punto de desaparecer y establecer asĂ nĂşcleos puros que permitieran desarrollar programas para su conservaciĂłn. Actualmente, estos animales se mantienen en centros de investigaciĂłn de AGROSAVIA gracias al apoyo del gobierno colombiano en sistemas de conservaciĂłn in vivo e in vitro. Desde su inicio, la estrategia de conservar estos nĂşcleos ha sido mantener la variabilidad genĂ©tica de las razas criollas y generar estrategias para fortalecer su conservaciĂłn, caracterizaciĂłn, promociĂłn y uso, sin dejar a un lado iniciativas que permitan incrementar la productividad animal y enfrentar los desafĂos como la intensificaciĂłn de los sistemas productivos, los efectos del cambio climático y los altos costos de mantenimiento en que incurre el Banco de Germoplasma Animal en Colombia. El Ă©xito de la conservaciĂłn de los recursos zoogenĂ©ticos en Colombia, dependerá en gran medida de la apropiaciĂłn y aceptaciĂłn de los productores colombianos para la inserciĂłn de estas razas en los sistemas de producciĂłn agropecuaria. Por otro lado, se requiere que el Banco de Germoplasma Animal incorpore otras especies o razas que se encuentran igualmente en peligro de desaparecer, y no cuentan con la protecciĂłn del gobierno local
A household case evidences shorter shedding of SARS-CoV-2 in naturally infected cats compared to their human owners
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected in domestic and wild cats. However, little is known about natural viral infections of domestic cats, although their importance for modelling disease spread, informing strategies for managing positive human-animal relationships and disease prevention. Here, we describe the SARS-CoV-2 infection in a household of two human adults and sibling cats (one male and two females) using real-time RT-PCR, an ELISA test, viral sequencing, and virus isolation. On May 5th, 2020, the cat-owners tested positive for SARS-CoV-2. Two days later, the male cat showed mild respiratory symptoms and tested positive. Four days after the male cat, the two female cats became positive, asymptomatically. Also, one human and one cat showed antibodies against SARS-CoV-2. All cats excreted detectable SARS-CoV-2 RNA for a shorter duration than humans and viral sequences analysis confirmed human-to-cat transmission. We could not determine if cat-to-cat transmission also occurred
No germline mutations in supposed tumour suppressor genes SAFB1 and SAFB2 in familial breast cancer with linkage to 19p
<p>Abstract</p> <p>Background</p> <p>The scaffold attachment factor B1 and B2 genes, <it>SAFB1/SAFB2 </it>(both located on chromosome 19p13.3) have recently been suggested as tumour suppressor genes involved in breast cancer development. The assumption was based on functional properties of the two genes and loss of heterozygosity of intragenic markers in breast tumours further strengthened the postulated hypothesis. In addition, linkage studies in Swedish breast cancer families also indicate the presence of a susceptibility gene for breast cancer at the 19p locus. Somatic mutations in <it>SAFB1/SAFB2 </it>have been detected in breast tumours, but to our knowledge no studies on germline mutations have been reported. In this study we investigated the possible involvement of <it>SAFB1/SAFB2 </it>on familiar breast cancer by inherited mutations in either of the two genes.</p> <p>Results</p> <p>Mutation analysis in families showing linkage to the <it>SAFB1/2 </it>locus was performed by DNA sequencing. The complete coding sequence of the two genes <it>SAFB1 </it>and <it>SAFB2 </it>was analyzed in germline DNA from 31 affected women. No missense or frameshift mutations were detected. One polymorphism was found in <it>SAFB1 </it>and eight polymorphisms were detected in <it>SAFB2</it>. MLPA-anlysis showed that both alleles of the two genes were preserved which excludes gene inactivation by large deletions.</p> <p>Conclusion</p> <p><it>SAFB1 </it>and <it>SAFB2 </it>are not likely to be causative of the hereditary breast cancer syndrome in west Swedish breast cancer families.</p
Sublittoral soft bottom communities and diversity of Mejillones Bay in northern Chile (Humboldt Current upwelling system)
The macrozoobenthos of Mejillones Bay (23°S; Humboldt Current) was quantitatively investigated over a 7-year period from austral summer 1995/1996 to winter 2002. About 78 van Veen grab samples taken at six stations (5, 10, 20 m depth) provided the basis for the analysis of the distribution of 60 species and 28 families of benthic invertebrates, as well as of their abundance and biomass. Mean abundance (2,119 individuals m-2) was in the same order compared to a previous investigation; mean biomass (966 g formalin wet mass m-2), however, exceeded prior estimations mainly due to the dominance of the bivalve Aulacomya ater. About 43% of the taxa inhabited the complete depth range. Mean taxonomic Shannon diversity (H', Log e) was 1.54 ± 0.58 with a maximum at 20 m (1.95 ± 0.33); evenness increased with depth. The fauna was numerically dominated by carnivorous gastropods, polychaetes and crustaceans (48%). About 15% of the species were suspensivorous, 13% sedimentivorous, 11% detritivorous, 7% omnivorous and 6% herbivorous. Cluster analyses showed a significant difference between the shallow and the deeper stations. Gammarid amphipods and the polychaete family Nephtyidae characterized the 5-mzone, the molluscs Aulacomya ater, Mitrella unifasciata and gammarids the intermediate zone, while the gastropod Nassarius gayi and the polychaete family Nereidae were most prominent at the deeper stations. The communities of the three depth zones did not appear to be limited by hypoxia during non-El Niño conditions. Therefore, no typical change in community structure occurred during El Niño 1997–1998, in contrast to what was observed for deeper faunal assemblages and hypoxic bays elsewhere in the coastal Humboldt Current system
Calibrating the Performance of SNP Arrays for Whole-Genome Association Studies
To facilitate whole-genome association studies (WGAS), several high-density SNP genotyping arrays have been developed. Genetic coverage and statistical power are the primary benchmark metrics in evaluating the performance of SNP arrays. Ideally, such evaluations would be done on a SNP set and a cohort of individuals that are both independently sampled from the original SNPs and individuals used in developing the arrays. Without utilization of an independent test set, previous estimates of genetic coverage and statistical power may be subject to an overfitting bias. Additionally, the SNP arrays' statistical power in WGAS has not been systematically assessed on real traits. One robust setting for doing so is to evaluate statistical power on thousands of traits measured from a single set of individuals. In this study, 359 newly sampled Americans of European descent were genotyped using both Affymetrix 500K (Affx500K) and Illumina 650Y (Ilmn650K) SNP arrays. From these data, we were able to obtain estimates of genetic coverage, which are robust to overfitting, by constructing an independent test set from among these genotypes and individuals. Furthermore, we collected liver tissue RNA from the participants and profiled these samples on a comprehensive gene expression microarray. The RNA levels were used as a large-scale set of quantitative traits to calibrate the relative statistical power of the commercial arrays. Our genetic coverage estimates are lower than previous reports, providing evidence that previous estimates may be inflated due to overfitting. The Ilmn650K platform showed reasonable power (50% or greater) to detect SNPs associated with quantitative traits when the signal-to-noise ratio (SNR) is greater than or equal to 0.5 and the causal SNP's minor allele frequency (MAF) is greater than or equal to 20% (N = 359). In testing each of the more than 40,000 gene expression traits for association to each of the SNPs on the Ilmn650K and Affx500K arrays, we found that the Ilmn650K yielded 15% times more discoveries than the Affx500K at the same false discovery rate (FDR) level
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