142 research outputs found
Uniform random generation of large acyclic digraphs
Directed acyclic graphs are the basic representation of the structure
underlying Bayesian networks, which represent multivariate probability
distributions. In many practical applications, such as the reverse engineering
of gene regulatory networks, not only the estimation of model parameters but
the reconstruction of the structure itself is of great interest. As well as for
the assessment of different structure learning algorithms in simulation
studies, a uniform sample from the space of directed acyclic graphs is required
to evaluate the prevalence of certain structural features. Here we analyse how
to sample acyclic digraphs uniformly at random through recursive enumeration,
an approach previously thought too computationally involved. Based on
complexity considerations, we discuss in particular how the enumeration
directly provides an exact method, which avoids the convergence issues of the
alternative Markov chain methods and is actually computationally much faster.
The limiting behaviour of the distribution of acyclic digraphs then allows us
to sample arbitrarily large graphs. Building on the ideas of recursive
enumeration based sampling we also introduce a novel hybrid Markov chain with
much faster convergence than current alternatives while still being easy to
adapt to various restrictions. Finally we discuss how to include such
restrictions in the combinatorial enumeration and the new hybrid Markov chain
method for efficient uniform sampling of the corresponding graphs.Comment: 15 pages, 2 figures. To appear in Statistics and Computin
Electrospun amplified fiber optics
A lot of research is focused on all-optical signal processing, aiming to
obtain effective alternatives to existing data transmission platforms.
Amplification of light in fiber optics, such as in Erbium-doped fiber
amplifiers, is especially important for an efficient signal transmission.
However, the complex fabrication methods, involving high-temperature processes
performed in highly pure environment, slow down the fabrication and make
amplified components expensive with respect to an ideal, high-throughput and
room temperature production. Here, we report on near infrared polymer fiber
amplifiers, working over a band of about 20 nm. The fibers are cheap, spun with
a process entirely carried out at room temperature, and show amplified
spontaneous emission with good gain coefficients as well as low optical losses
(a few cm^-1). The amplification process is favoured by the high fiber quality
and low self-absorption. The found performance metrics promise to be suitable
for short-distance operation, and the large variety of commercially-available
doping dyes might allow for effective multi-wavelength operation by electrospun
amplified fiber optics.Comment: 27 pages, 8 figure
An abrupt weakening of the subpolar gyre as trigger of Little Ice Age-type episodes
We investigate the mechanism of a decadal-scale weakening shift in the strength of the subpolar gyre (SPG) that is found in one among three last millennium simulations with a state-of-the-art Earth system model. The SPG shift triggers multicentennial anomalies in the North Atlantic climate driven by long-lasting internal feedbacks relating anomalous oceanic and atmospheric circulation, sea ice extent, and upper-ocean salinity in the Labrador Sea. Yet changes throughout or after the shift are not associated with a persistent weakening of the Atlantic Meridional Overturning Circulation or shifts in the North Atlantic Oscillation. The anomalous climate state of the North Atlantic simulated after the shift agrees well with climate reconstructions from within the area, which describe a transition between a stronger and weaker SPG during the relatively warm medieval climate and the cold Little Ice Age respectively. However, model and data differ in the timing of the onset. The simulated SPG shift is caused by a rapid increase in the freshwater export from the Arctic and associated freshening in the upper Labrador Sea. Such freshwater anomaly relates to prominent thickening of the Arctic sea ice, following the cluster of relatively small-magnitude volcanic eruptions by 1600 CE. Sensitivity experiments without volcanic forcing can nonetheless produce similar abrupt events; a necessary causal link between the volcanic cluster and the SPG shift can therefore be excluded. Instead, preconditioning by internal variability explains discrepancies in the timing between the simulated SPG shift and the reconstructed estimates for the Little Ice Age onset
Low-risk susceptibility alleles in 40 human breast cancer cell lines
Background: Low-risk breast cancer susceptibility alleles or SNPs confer only modest breast cancer risks ranging from just over 1.0 to 1.3 fold. Yet, they are common among most populations and therefore are involved in the development of essentially all breast cancers. The mechanism by which the low-risk SNPs confer breast cancer risks is currently unclear. The breast cancer association consortium BCAC has hypothesized that the low-risk SNPs modulate expression levels of nearby located genes. Methods: Genotypes of five low-risk SNPs were determined for 40 human breast cancer cell lines, by direct sequencing of PCR-amplified genomic templates. We have analyzed expression of the four genes that are located nearby the low-risk SNPs, by using real-time RT-PCR and Human Exon microarrays. Results: The SNP genotypes and additional phenotypic data on the breast cancer cell lines are presented. We did not detect any effect of the SNP genotypes on expression levels of the nearby-located genes MAP3K1, FGFR2, TNRC9 and LSP1. Conclusion: The SNP genotypes provide a base line for functional studies in a well-characterized cohort of 40 human breast cancer cell lines. Our expression analyses suggest that a putative disease mechanism through gene expression modulation is not operative in breast cancer cell lines
Evaluation of the performance of Dutch Lipid Clinic Network score in an Italian FH population: The LIPIGEN study
Background and aims: Familial hypercholesterolemia (FH) is an inherited disorder characterized by high levels of blood cholesterol from birth and premature coronary heart disease. Thus, the identification of FH patients is crucial to prevent or delay the onset of cardiovascular events, and the availability of a tool helping with the diagnosis in the setting of general medicine is essential to improve FH patient identification.Methods: This study evaluated the performance of the Dutch Lipid Clinic Network (DLCN) score in FH patients enrolled in the LIPIGEN study, an Italian integrated network aimed at improving the identification of patients with genetic dyslipidaemias, including FH.Results: The DLCN score was applied on a sample of 1377 adults (mean age 42.9 +/- 14.2 years) with genetic diagnosis of FH, resulting in 28.5% of the sample classified as probable FH and 37.9% as classified definite FH. Among these subjects, 43.4% had at least one missing data out of 8, and about 10.0% had 4 missing data or more. When analyzed based on the type of missing data, a higher percentage of subjects with at least 1 missing data in the clinical history or physical examination was classified as possible FH (DLCN score 3-5). We also found that using real or estimated pre-treatment LDL-C levels may significantly modify the DLCN score.Conclusions: Although the DLCN score is a useful tool for physicians in the diagnosis of FH, it may be limited by the complexity to retrieve all the essential information, suggesting a crucial role of the clinical judgement in the identification of FH subjects
Expression profiling of familial breast cancers demonstrates higher expression of FGFR2 in BRCA2-associated tumors
BackgroundBRCA1- and BRCA2-associated tumors appear to have distinct molecular signatures. BRCA1-associated tumors are predominantly basal-like cancers, whereas BRCA2-associated tumors have a predominant luminal-like phenotype. These two molecular signatures reflect in part the two cell types found in the terminal duct lobular unit of the breast. To elucidate novel genes involved in these two spectra of breast tumorigenesis we performed global gene expression analysis on breast tumors from germline BRCA1 and BRCA2 mutation carriers. Methodology Breast tumor RNAs from 7 BRCA1 and 6 BRCA2 mutation carriers were profiled using UHN human 19K cDNA microarrays. Supervised univariate analyses were conducted to identify genes differentially expressed between BRCA1 and BRCA2-associated tumors. Selected discriminatory genes were validated using real time reverse transcription polymerase chain reaction in the tumor RNAs, and/or by immunohistochemistry (IHC) or by in situ hybridization (ISH) on tissue microarrays (TMAs) containing an independent set of 58 BRCA1 and 64 BRCA2-associated tumors. Results Genes more highly expressed in BRCA1-associated tumors included stathmin, osteopontin, TGFβ2 and Jagged 1 in addition to genes previously identified as characteristic of basal-like breast cancers. BRCA2-associated cancers were characterized by the higher relative expression of FGF1 and FGFR2. FGFR2 protein was also more highly expressed in BRCA2-associated cancers (P = 0.004). SignificanceBRCA1-associated tumours demonstrated increased expression of component genes of the Notch and TGFβ pathways whereas the higher expression of FGFR2 and FGF1 in BRCA2-associated cancers suggests the existence of an autocrine stimulatory loop
- …